Physiology exam 2 notes.pdf

Topic 06: Chemical Messengers Chemical Communication Endocrine system: hormones as chemical messengers Nervous system: neurotransmitters as chemical messengers Endocrine system vs. Nervous system o Both act as transducers, receiving information from one system and...

Topic 06: Chemical Messengers Chemical Communication Endocrine system: hormones as chemical messengers Nervous system: neurotransmitters as chemical messengers Endocrine system vs. Nervous system o Both act as transducers, receiving information from one system and transmit it o Nervous system à faster § Alters how neighboring neurons behave o Endocrine system à acts over a longer range in the body & long-lasting e?ect § Alters how multiple organs function in the body Chemical Messengers Hormone: travels through bloodstream; target cells in distant places Neurotransmitters: direct cell to cell communication; in close proximity Paracrine substance: target cells near the site of paracrine substance release Autocrine substance: same cell produces signal and response A substance can become more than just one type of messenger o Ex- norepinephrine: both hormone and neurotransmitter Receptors Receptors: where chemical messengers bind Chemical messenger must bind to receptor à response Cells with the same receptor can have di?erent responses o It depends on: § Cell type § Type of intracellular proteins activated by the receptor § Other signals a?ecting the cell simultaneously Same receptor but di?erent intracellular protein à di?erent cellular response Di?erent receptors à di?erent cellular response 1. Water-soluble Chemical Messenger o They can’t di?use across cell membrane o Bind to receptors on the cell surface = transmembrane protein o Receptors activate other proteins in cell = transduction o Faster response § Because it alters the activity of existing proteins o Notable types § Ligand-gated ion channels  Ligand binds to receptor à channel opens à increased cell permeability to ion à cellular response induced inside the cell o Ex- ligands like serotonin and neurotransmitter § G Protein-coupled receptors Ligand binds to receptor à activates G protein (helps it bind GTP) à G protein activates adenylyl cyclase enzyme à adenylyl cyclase makes cAMP from ATP à cAMP activates kinase à kinase phosphorylates other proteins à include cellular response o Ex- ligand like epinephrine hormone Signal Amplification o cAMP produce à signal amplification § one molecule of first messenger à many cAMP molecules (second messenger) à many active kinases o Amplification: allows fast & complex cell response o Ex- 1 molecule of epinephrine bound à 108 molecules of glucose released in liver 2. Lipid-soluble chemical messenger o They can di?use across cell membrane o Bind to receptors inside the cell (in cytosol/nucleus) o Receptor binds to specific noncoding sequences in DNA à changes gene expression o Slower & more long-lasting response § Because it results in the synthesis of new proteins o Notable type § Receptors functioning as Kinases Ligand binds to receptor à phosphorylation cascade à include cellular response o Ex- ligand like insulin hormone Topic 07: Endocrine System Exocrine vs. Endocrine Glands Exocrine: secrete substances into ducts/tubes o Ex- sweat gland, gallbladder Endocrine: secrete substances into bloodstream o Ex- pineal gland: secreting melatonin into bloodstream Some organs have both endocrine and exocrine functions o Ex- pancreas Hormone Mechanisms of Action Water-soluble hormone  o Binds to cell surface receptors o Alter activity of existing proteins à faster response produced than lipid-soluble hormone o May a?ect synthesis of new proteins (change gene expression) Fat-soluble hormone o Binds to intracellular receptor o Increase/decrease synthesis of new proteins (change gene expression) o Require carrier protein for transport in blood o New hormone synthesized, transcription and translation take time à longer time for response Chemical Classes of Hormones Amino acid derivatives o Most of them are not lipid soluble o Binds to receptors on surface of target cell § Ex- epinephrine, tyrosine Polypeptide o They are not lipid soluble o Binds to receptors on surface of target cell § Ex- secretin Steroids o They are lipid soluble o Often binds to receptors inside target cell § Ex- cholesterol, cortisol Amine hormone o Made from tyrosine amino acid o 2 types: § Catecholamines Made by modifying side groups of tyrosine Polar; cell surface receptors; adrenal medulla (of adrenal gland) Ex- epinephrine & norepinephrine § Thyroid hormones Made from two tyrosines and iodine atoms Slightly polar; intracellular receptors; thyroid gland Ex- T3 & T4 o Each gland has di?erent enzymes used to make di?erent hormones § Ex- adrenal gland can make epinephrine but not T3 because it has enzymes to catalyze the synthesis of epinephrine Peptide and Protein hormone o Most hormones in this category § Ex- insulin, ACTH, TSH o Large, generally polar; cell surface receptors o Made through transcription and translation (encoded by a gene) § Many are made as a longer protein, but are cut into smaller, biologically active peptide § Secreted via exocytosis Steroid hormone o Made from cholesterol o Nonpolar; intracellular receptors; adrenal cortex, gonads o Synthesized when another hormone binds to endocrine cell GPCR à activates steroid synthesis enzymes o Secreted via di?usion (due to being small, nonpolar) o Hormone synthesis § By adrenal gland Adrenal cortex (outer) o Corticosteroid (steroid hormones) § Aldosterone (blood osmolarity) § Cortisol (stress, metabolism) Adrenal medulla (inner) o Catecholamines (amine hormones)  § Epinephrine § Norepinephrine Di?erent parts of the adrenal glands produce di?erent hormones because they express di?erence enzymes for each synthesis § By gonads Androgens: testosterone Estrogens: estradiol o Both sex hormones can be produced by men and women, but in di?erent ratios o Ovaries produce more aromatase because they convert more testosterone to estradiol o Transport § By carrier proteins Albumin, binding globulins o Ex- corticosteroid-binding globulin, thyroxine-binding globulin (binds T4) o Because steroids = nonpolar, not soluble in blood o Hormone detached from the carrier when getting into target cell Endocrine System Regulation Outline Need to regulate: o When and how much hormone is synthesized/secreted o How long hormone persists in the bloodstream/body o Whether cells respond to it (sensitivity to hormone) § Sensitivity = based on whether a specific receptor is present or not Regulating hormone synthesis/secretion o Three main inputs: § Ions/nutrients Change in concentration stimulates hormone production/secretion o Ex- glucose and insulin/glucagon § High glucose à insulin released § Low glucose à glucagon released o Ex- calcium and parathyroid hormone § Low calcium level à parathyroid hormone released § Neurons Activate/inhibit hormone synthesis/release from gland o Sympathetic nervous system and adrenal medulla § Other hormones Tropic hormones from hypothalamus and pituitary stimulate synthesis/release of hormone from other glands o Ex- CRH à triggers pituitary gland à release ACTH à trigger adrenal cortex à release cortisol o Ex- TRH à stimulate pituitary gland à release TSH à binds to the receptors on thyroid gland à release thyroid hormone Hormone metabolism & excretion o Not all hormone circulating in blood go to target cells § Some metabolized (can be activated or inactivated by metabolism) Activated à go to target cell § Some excreted in urine or feces § Some go straight to the target cell o Half-life = indicate time it takes for half of the hormone to be cleared from bloodstream (figure out how long hormone lasts in bloodstream) § Cortisol half-lie = about 1 hour  § Epinephrine half-life = about 1 minute Regulation of hormone receptors o Cell’s ability to respond to hormone depends on the presence of specific receptors for the hormone o To increase cell’s sensitivity to hormone à more receptors should be synthesized = up-regulation § Exocytosis of cell-surface receptors à more receptors on cell surface o To decrease cell’s sensitivity to hormone à degrade existing receptors, decrease synthesis of receptors = down- regulation § Endocytosis of vesicles containing receptor à receptors removed from cell surface o Endocytosed receptors can recycled as exocytosed receptor Endocrine Disorders Hyposecretion o Do not make enough hormones § Ex- type I diabetes § Ex- dwarfism = hyposecretion of GH Hyporesponsiveness o Make enough hormone, but do not respond to it § Ex- type II diabetes Hypersecretion o Make too much hormone § Ex- hyperthyroidism § Ex- gigantism = hypersecretion of GH Hyperresponsiveness o Cell respond excessively to normal amount of hormone o Cause: target cells make too much receptors Pharmacological EBects of Hormone Birth control o Increases level of estrogen and progesterone à mimicking pregnant state Corticosteroids o For allergies/inflammation o Synthetic version of cortisol Hormone replacement o For menopause o Estrogen drops dramatically à can make it gradual by taking estrogen Anabolic steroids o For bodybuilding o Bodybuilding: testosterone stimulates protein synthesis o Used for muscle replacing Thyroid hormone o For people with hypothyroidism Hypothalamus and Pituitary Gland Regulating Hormone Production Hypothalamus (hypophysis) o Contains neuro-secretory cells: neurons that make hormones o Connected to pituitary gland by infundibulum (contains axons and blood vessels) o Releases hormones into: § Posterior pituitary § Blood vessels à go to anterior pituitary Posterior pituitary gland o Contains axon terminals of hypothalamic neurons o Hormones synthesized in hypothalamus (specifically in cell bodies of hypothalamic neurons) o Hormones released by posterior (specifically axon terminals of hypothalamic neurons) § Not the site of synthesis; just a site of release into blood; can’t make own hormone o Hormones § Oxytocin Regulates reproduction and social behavior; milk production, reinforce social bonding § Antidiuretic hormone (ADH)  Regulate blood osmolarity (primarily a?ect cells in kidney where receptors for ADH are present) Anterior pituitary gland o Makes its own hormones o Released only in response to hypophysiotropic from hypothalamus o Synthesizes tropic hormones that regulate function of other endocrine glands § Ex- TSH, ACTH Hypothalamic-pituitary-adrenal Axis (HPA Axis) 1. Stress triggers hypothalamus 2. Hypothalamus: release corticotropin-releasing hormone (CRH) 3. CRH binds to the receptor on anterior pituitary 4. Anterior pituitary: release adrenocorticotropic hormone (ACTH) 5. ACTH binds to the receptor on adrenal cortex 6. Adrenal cortex: releases cortisol 7. Negative feedback: cortisol binds to receptors in anterior pituitary and hypothalamus à ACTH & CRH production inhibited Physiological Functions of Cortisol Regulates metabolism and maintains glucose levels o Stimulates gluconeogenesis o Stimulate catabolism of fats and proteins Regulates immune system o Suppresses inflammation o Prevents autoimmunity § Too much cortisol suppresses immune system = why people get sick when stressed Maintains blood pressure Regulates sleep/wake cycle o Lower à around sleep time o Higher à when awake Important for development Increases during stress Two System Respond to Stress: Sympathetic NS and HPA axis Short-term stress response and adrenal medulla (sympathetic NS) o Epinephrine and norepinephrine release § Glycogenolysis: glycogen broken down to glucose; increased blood glucose § Increased blood pressure § Increased breathing rate § Increased metabolic rate § Change in blood flow patterns (route more blood with O2 and nutrients to tissues, helping fight the stress), leading to increased alertness and decreased digestive, excretory reproductive system activity Long-term stress response and the adrenal cortex (HPA axis) o Release cortisol: part of glucocorticoids o Glucocorticoids § Proteins and fats broken down and converted to glucose, leading to increased blood glucose § Partial suppression of immune system Immune system = energetically demanding à suppressing will save energy  § Glycogen quickly used up from short-term stress response à cortisol used to prolong response to stress by making glucose available longer Diseases ABecting Cortisol Levels Cortisol hyposecretion o Due to infections/cancers that destroy adrenal cortex cells o Due to hyposecretion of ACTH by anterior pituitary § Ex- Addison’s disease Symptoms: weakness, weight loss, autoimmune disease Cortisol hypersecretion o Due to tumor in adrenal cortex that over secrets cortisol o Hypersecretion of ACTH by anterior pituitary § Ex- Cushing’s disease Symptoms: hyperglycemia, abdominal obesity, immunosuppression Hypothalamic-pituitary-thyroid Axis (HPT Axis) T4 is converted to T3 by deiodinase T3 binds to intracellular receptors E?ects of T3: increase metabolism and body heat o Increase absorption of carbohydrates o Increase lipid catabolism o Increase mitochondria o Stimulate Na+/K+ pumps Deficiencies during development impair growth and nervous system Diseases ABecting Thyroid Levels Hypothyroidism o Symptoms: cold intolerance, weight gain, fatigue, depression o Treatment: give patients synthetic thyroid hormones Hyperthyroidism o Symptoms: heat intolerance, weight loss, increased appetite, anxiety o Treatment: thyroid gland removed, inhibitors of T4 synthesis enzyme, radioactive iodine Goiter o It is overgrowth of thyroid gland o Caused by TSH hypersecretion & iodine deficiency Endocrine Control of Ca2+ Homeostasis Why control extracellular levels of Ca2+?  o Ca2+ plays important roles in neuron signaling and muscle contraction Regulation of blood Ca2+ levels o Bone: stores 99% of body calcium § Osteoblasts: take up Ca2+ from blood and use it to build bone § Osteoclasts: break down (consume) bone = resorption; to release Ca2+ into blood o Gastrointestinal tract § Absorbs Ca2+ from food o Kidneys § Reabsorb Ca2+ into blood (reduces its excretion All three regulations under endocrine control o Parathyroid hormone (PTH) o Vitamin D Parathyroid Hormone (PTH) Made by 4 parathyroid glands PTH secretion triggered by decreased blood Ca2+ level Stimulates: o Activity of osteoclasts (Ca2+ release from bone) o Kidney reabsorption and reduced excretion of Ca2+ o Kidney production of vitamin D o Absorption of Ca2+ from food (in presence of vitamin D) Synthesis of Vitamin D Sunlight converts a steroid molecule in the skin to vitamin D (inactive) Liver converts vitamin D from skin and diet à another molecule = 25(OH)D (calcidiol) Kidney converts this to biologically active vitamin D = 1,25(OH)2D (calcitriol) o PTH stimulates kidney’s production of the enzyme for this step Biologically active vitamin D increase absorption of Ca2+ from food o Mechanism: increase expression of genes encoding Ca2+ channels and pumps in intestinal cells When blood calcium level gets too high à PTH and vitamin D should not be released Topic 08: Nervous System Two major divisions: central nervous system & peripheral nervous system Main cell types: neurons & Glia Nucleus/nuclei: refers to a group of neurons within the CNS; could be within the brain or spinal cord Ganglion/ganglia: refers to a group of neurons outside the CNS Nerve: refers to a group of axons outside the CNS Cells of the Nervous System Cell body with nucleus Dendrite Axon ends in axon terminal Neurons make up ~10% of nervous system o Don’t divide when mature § Only things that change as adult is connections between neurons that are existing o High metabolic rate  § Rely on glucose a lot; ketone also usable § Neurons maintain high rates of cellular respiration because they need a lot of ATP for primary active transport of ions (Na+/K+ & Ca2+ pumps); and for synthesis and exocytosis of neurotransmitters Other ~90% of nervous system made up of glia o Provide physical and metabolic support Glia Cells In CNS o Astrocytes: support neurons and make blood-brain barrier § Fatty acids can’t cross blood-brain barrier; glucose, oxygen, ketones can; because fatty acids can’t cross, ketones are made so that neurons can use them for energy when glucose levels are low o Microglia: remove pathogens and waste § Do phagocytosis to defend CNS cells o Ependymal cells: produce cerebrospinal fluid o Oligodendrocytes: myelinate axons In PNS o Satellite cells: support neurons (make sure they are getting oxygen and nutrients needed) o Schwann cells: myelinate axons Myelin It is layers of modified plasma membrane wrapped around the axon of a neuron; prevent neuron from being exposed to extracellular fluid Functions: o Insulate axon to conduct information more quickly § Information in the form of ions di?using through axons; coating axons à makes ions move faster without leaking out of the membrane o Protect axon from damage § Multiple sclerosis: disease in which immune system attacks myelin; thinking it is a foreign system and destroy it Motor neuron stop working quick enough à issues with movement of muscles o Could be treated with corticosteroids (can suppress immune system and reduce inflammation Made by 2 types of glial cells o Schwann cells (PNS) o Oligodendrocytes (CNS) White vs. Grey matter o White: myelinated axons of neurons o Grey: cell bodies of neurons Synapses (communication) It is location where two neurons communicate In here, neurotransmitters are released = information is transmitted from one neuron to another Cells are referred to by their position in relation to the synapse o Presynaptic neuron: releases NT (sending information) o Postsynaptic neuron: responding to NT (receiving information from dendrite to axon) Functional Classes of Neurons A?erent neurons: transmit information from PNS to CNS (communicating to spinal cord or brain) Interneurons: transmit information within the CNS (communicating to either spinal cord or brain); majority of neurons in the body are this E?erent neurons: transmit information from CNS to PNS; motor neurons o Mnemonic: SAME (sensory a?erent motor e?erent) Membrane Potential It is di?erence in electrical charge across a cell membrane in neurons Due to di?erence in charged ion concentration inside vs. outside cell o Inside more negative relative to outside § Large negatively charged nonpenetrating ions inside cytosol relative to outside § More positive ions outside than inside Types of membrane potential o Resting potential o Graded potential o Action potential Resting Membrane Potential At rest, cells are negatively charged inside relative to outside (extracellular fluid) Membrane is said to polarized o For most neurons, resting potential = around -70mV Due to main 2 factors: o Many large negatively charged molecules inside the cell (DNA, RNA, PO43-) o Na+/K+ pump (electronic) o Ungated (“leak”) K+ channels Opening of gated ion channels causes a change in membrane potential (graded/action potential) Establishing Resting Membrane Potential Set up in 2 ways: o Active transport by Na+/K+ pump § Pumps 3 Na+ out of cell § Pumps 3 K+ into cell § Results in more positive ions moving out than brought in à inside of the cell becomes a bit more negatively charged than outside overtime o Involve facilitated di?usion through leak (ungated) channels § Neurons have more K+ leak channels and fewer Na+ leak channels à more K+ leave the cell than Na+ coming into the cell; losing more positive ions than gaining over time § Results in more positive ions leave cell than come in Changes in Membrane Potential Caused by opening and closing of gated ion channels 2 types of changes o Graded potential: small, localized change in membrane potential o Large, “all or none” change in membrane potential Depolarization: potential becomes less negative/more positive o Ex- in Na+/K+ pump, would be caused by opening gated Na+ channels (flowing into the cell à more positive) Hyperpolarization: potential becomes more negative o Ex- in Na+/K+ pump, would be caused by opening gated K+ channels (flowing out of the cell à more negative) Graded Potential It is transient change in membrane potential, confined to small region of plasma membrane usually on dendrites Only few ion channels open Usually involves ligand-gated ion channels or mechanically-gated ion channels May be depolarizing/hyperpolarizing (depends on the type of channel) Dissipates quickly due to leak channels and Na+/K+ pump Action Potential It is large, “all or none” change in membrane potential o Fast (milliseconds), can repeat Triggered by depolarization to a “threshold” caused by graded potential Involved opening of many voltage gated channels o Voltage-gated Na+ channels à cause depolarization o Voltage-gated K+ channels à cause repolarization and hyperpolarization Other channels involved in neuron signaling o Voltage-gated Ca2+ channels à help stimulate neurotransmitter release Voltage-gated Channels & Action Potentials Na+ channels: undergo 3 states: closed, open, inactivated o Opens in response to depolarization to threshold caused by ligand-gated or mechanically-gated ion channels o Inactivated after membrane potential becomes positive o Inactivation lasts until membrane potential returns to resting o At that point, channels are closed but capable of re-opening K+ channels: undergo 2 states (closed, open) o Opens in response to depolarization to threshold caused by ligand-gated/mechanically-gated ion channels o Closes in response to membrane potential returning to resting o Major di?erence compared to Na+ channels: § Speed of opening/closing Stimuli for opening and closing for K+ and Na+ channel is same but K+ channels work more slowly o K+ channels work more slowly § They don’t all end up opening until cell reaches peak of action potential § Don’t close until after cell returns to resting Activation gate: positively charged Inactivation gate: negatively charged  Stimulus causes membrane potential to be more positive Positive charge inside the cell à charge of the gate also positive à charge builds up à positively charged gate opened à inactivation gate automatically closes Only way to re-stimulate the channel: needs to be rest to closed state Second phase of action potential happens à K+ rushed out of the cell à cell becomes more negative à activation gate pulled in and channel closes (both gates closed = ready to start another action potential) Action Potential Summary Cell is at resting potential; all gated channels are closed Ligand-gated Na+ channels open à Na+ flows into cell o Enough Na+ comes in à cell may depolarize to threshold (-55mV) o Permeability to Na+ starts to rise; permeability to K+ stays the same Voltage-gated Na+ channels open o Na+ flows in; cell becomes depolarized even more à opens more Na+ channel (positive feedback à rapid rise in membrane potential to positive) o Permeability to Na+ higher at #3 stage Voltage-gated Na+ channels inactive o Stop depolarizing because Na+ channels inactivated à no more Na+ can come in Voltage-gated K+ channels open o K+ flows out of cell: repolarize back to resting potential o K+ channels must be opened more slowly than Na+ channels § Because both channels triggered by same stimulus (depolarization to threshold) à open at the same time à Na+ moving in, K+ moving out simultaneously à no net change in voltage à not action potential Voltage-gated K channels close slowly + o K+ keeps flowing out of cell until all channels close = hyperpolarization § K+ leaks out even after channel closes à K+ permeability declines very slowly o By the time all K+ channels are closed, more K+ left the cell à membrane voltage goes below resting potential (around - 80mV) Returns to resting potential o Due to Na+/K+ pump, rebalances the ion concentration inside the cell § At the end of action potential (at resting membrane voltage), concentrations of Na+ and K+ di?erent from the start Before: low Na+, high K+ in cytosol relative to outside During action potential: a lot of Na+ came into the cell; a lot of K+ left the cell End: high Na+, low K+ in cytosol relative to outside o But starts and ends at the same voltage; but concentration of Na+ and K+ is flipped § For the relative membrane permeability graph In the beginning: permeability for K+ slightly higher o Because neuron has more leak channels for K+ than for Na+ à K+ leaves cell and keep membrane potential relatively at rest Control Mechanism  Na+ channel opening o Channel open à depolarization à more channels open à more depolarization o Type of feedback: positive feedback à increases depolarization K+ channel opening o Channel open à repolarization à channels close o Type of feedback: negative feedback à causes repolarization and hyperpolarization Threshold Stimuli & Action Potentials 1. Threshold stimulus: a stimulus that causes a graded potential that reaches threshold for AP 2. Threshold potential: membrane potential that is at threshold for AP 3. Subthreshold stimulus: a stimulus that causes a graded potential that doesn’t reach threshold 4. Subthreshold potential: membrane potential that is below threshold for AP a. Once you hit threshold stimulus, any stimuli that are stronger than a threshold stimulus will cause same action potential (last four action potentials on the top graph) b. If AP is all or nothing, how do you distinguish between a strong stimulus and weak stimulus (eg. Tap from a pinch)? i. Stronger stimulus triggers more action potentials in the same amount of time (higher frequency) than a weaker stimulus (may keep the cell above the threshold potential longer) ii. All about frequency of APs (as all APs are same magnitude) iii. Stronger stimulus elicits more APs Action Potential Inhibition Action potentials that produce pain sensations can be prevented by local anesthetics o ex- Novocaine, Iidocaine o Method: § Block voltage-gated Na+ channels § How does stop pain? Na+ ions can’t come in, prevents APs in sensory neuron = pain message doesn’t reach brain § Ex- Tetrodotoxin It is a natural voltage-gated Na+ channel blocker Produced by pu?erfish Refractory Period Time after an AP during which it is impossible (absolute) or very di?icult (relative) to trigger another AP Absolute refractory period: when voltage gated Na+ channels start opening and to when the cell returns back to resting potential o Time during which another stimulus (no matter how strong) will nor produce another AP o Because all voltage-gated Na+ channels already open or all voltage-gated Na+ channels inactivated Relative refractory period: time during which another AP can be produced only if stimulus is much stronger than usual o Because cell is hyperpolarized because some K+ is still flowing out (channels close slowly) o Graded potential has to be bigger to depolarize from hyperpolarized to threshold § At relative refectory period, graded potential has to be higher than the initial to reach threshold  § At relative refractory period, voltage-gated K+ channels are open at this time (voltage-gated Na+ channels have reset from inactivated to closed) Normal action potential caused by regular stimulus Shorter the bar weaker the stimulus vice versa Absolute refectory period: strongest stimulus possible, but don’t cause another action potential As soon as you hit resting potential, hyperpolarization happens and is considered relative refractory period As K+ channel starts to close, stimulus required to reach threshold can be a little smaller in hyperpolarization phase When back to resting potential à doesn’t take much to each action potential Refractory period is important because it limits how many action potentials a cell can do in a given time; mainly in how it regulates how action potentials propagate along axons of neurons AP Propagation Generally dendrites and cell body membrane of neurons will contain ligand-gated or mechanically gated ion channels Refractory period makes APs unidirectional o Cell body à axon à axon terminals During an AP, Na+ ions di?use inside neuron to neighboring parts of membrane in both directions o Can depolarize neighboring regions of membrane o Part of membrane ahead of where AP is happening § Can be depolarized to threshold à trigger AP there o Part of membrane just behind where AP is happening § It is in refractory period à can’t cause another AP AP Propagation & Myelin Myelin covers membrane and prevents ions coming into/out of axon o Completely impermeable to ions Only places where ions can go in/out are nodes of Ranvier = unmyelinated gaps of exposed membrane along axon Myelin speeds up propagation of AP along the axon o Because it has less membrane to depolarize (only at nodes of Ranvier) o Fewer places for ions to leak out and weaken the current o Fewer Na+/K+ pumps needed to restore resting potential Action potential propagates faster through an axon with 15 nodes of Ranvier or 12? o Faster with 12 nodes; since each node is an area where Na+ ions can leak out and be pumped out by Na+/K+ pump, more exposed membrane à slow down action potential propagation o Depolarization doesn’t occur at myelinated area This mechanism is saltatory conduction: conduction through myelinated nerve fiber o In ion-myelinated neuron, each region do the membrane needs to be depolarized; so it’s going to take some time for action potential to reach the axon terminal o In a myelinated neuron, it skips area that’s myelinated and action potential reaches the axon terminal much faster What Happens When It Reaches the Axon Terminal? At synapse o Most synapses are chemical synapses § Presynaptic neuron releases NT from axon terminal exocytosis § NT binds to ligand-gated ion channels on postsynaptic neuron’s membrane § E?ect: open ion channels, which lead to a graded potential (may or may not lead to action potential) o Some synapses are electrical synapses § Membrane is connected by gap junctions, ions flow directly between cells § Speed of transmission = faster than chemical synapses § Used by some neurons and cardiac muscle Neurotransmitter Release AP arrives at axon terminal depolarizes membrane o When membrane of action terminal is depolarized = stimulus to open voltage-gated Ca2+ channels Voltage-gated Ca2+channels open (a lot of primary active transport out of the cytosol à Ca2+ kept at low level inside axon terminal by calcium pump à has much higher concentration outside the cell à flows into the cell o Axon terminals would have voltage-gated Na+ and K+ channels for action potential; voltage-gated Ca2+ channels; but no ligand-gated ion channels which are found mainly on dendrites Ca2+ moves from high to low concentration into the cell Ca2+ triggers exocytosis of vesicles containing NT NT di?uses across synapse (Red dots on the image), binds to ligand-gated ion channels (like Na+ channels) on postsynaptic neuron NT is removed from synapse Why is Ca2+ needed? o Vesicles with NTs are tethered to presynaptic neuron’s membrane with proteins called SNAREs o Vesicle loosely connected in the absence of calcium à Ca2+ concentration increases à binds to SNAREs à conformational change of tightening two twisters around the vesicle à fuse into membrane to release NT into synapse Synaptic Cleft Neurotransmitters are removed from synapse by: o Reuptake into presynaptic neuron (recycling) o Degradation by enzymes made by postsynaptic neuron o Di?usion away from the synapse (often glial cells help get rid of excess NT) Why does NT need to be removed? o NT release is a transient signal (short-lived, fast); don’t want to overstimulate post-synaptic neuron EBect of Drugs on Synapses A drug might: o Increase leakage of NT from vesicle to cytoplasm, exposing it to enzyme breakdown à NT can’t properly be secreted by exocytosis à decreased communication between the presynaptic and postsynaptic neuron o Increase transmitter release into cleft à increase communication because more NT released o Block transmitter release à decreased communication because exocytosis blocked  o Inhibit transmitter synthesis à decreased communication because NT can’t be released o Block transmitter reuptake à increased communication because NT will stay longer in synapse à keep binding to receptors in postsynaptic neuron à more communication o Block cleft or intracellular enzymes that metabolize transmitter à increased communication; keep binding to receptors in postsynaptic neuron à more communication o Bind to receptor on postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action à antagonist would decrease communication; agonist would increase communication o Inactivated/blocked voltage-gated Ca2+ channels in presynaptic neuron à decrease communication because Ca2+ won’t be able to come into axon terminal, bind to SNAREs, and trigger exocytosis of NT vesicles Neurotransmitter EBects on Postsynaptic Cell NT may be excitatory or inhibitory Excitatory postsynaptic potential (EPSP) o Caused by excitatory neurotransmitter § Ex- glutamate, acetylcholine o Makes membrane potential more positive, closer to threshold for action potential o Type of ion channels opened: § Bind to ligand-gated Na+ channels Because of the gradient established by Na+/K+ pump, Na+ ions want to come into the cell à opening Na+ channel à Na+ flows into the cell by facilitated di?usion down the concentration gradient à depolarize the cell Inhibitory postsynaptic potential (IPSP) o Makes membrane potential more negative, harder to elicit future APs o Caused by inhibitory neurotransmitter § Ex- serotonin, GABA o Type of ion channels opened: § Ligand-gated K+ channels § Ligand-gated Cl- channels Flow into the cell (high to low) à negative ions flow in à membrane potential become negative à moves further from eliciting AP Neurotransmitters EBects on Postsynaptic Cell Most neurons have multiple synapses o 7000 to 10,000+ synapses per neuron Post-synaptic neurons have to integrate information arriving from di?erent synapses = synaptic summation Synaptic Summation One EPSP is not enough to reach threshold and trigger AP If more EPSPs occur before neuron has time to repolarize, can open more Na+ channels à more depolarization à threshold for AP EPSPs and IPSPs may occur in same neuron and cancel each other out Temporal summation o Same presynaptic neurons send multiple signals back to back o NTs released multiple times from same synapse close in time back to back Spatial summation o Several di?erent presynaptic neurons send signals at the same time  o NTs from multiple synapses (points in spaces) released at the same time (same time, multiple location) Scenario 4 = both temporal and spatial summation o Presynaptic neuron A sends 2 signals back to back around the same time presynaptic neuron B does the same thing = temporal summation (close in time) and spatial summation (from 2 separate neurons) Scenario 5 = spatial summation between excitatory and inhibitory synapses o C à hyperpolarization o Excitatory (A) and inhibitory (C) at the same time à cancels each other out § Do this because under time of extreme stress, body will block any pain signals reaching the brain In order to reach enough threshold, both temporal and spatial summation must be done Classes of Neurotransmitters Acetylcholine o Used in both PNS and CNS by cholinergic neurons o Made by combining acetyl CoA and Choline o Types of: § Nicotinic: ligand-gated ion channels Used by some neurons Triggers contraction of skeletal muscle § Muscarinic: G protein-coupled receptors NT binds to GPCR à G protein binds to GTP à activated; G protein serves as the ligand-gated ion channel à opening the channel Used by parasympathetic NS, brain, smooth and cardiac muscle Slows heart rate (by slowing pacemaker/node of heart) § Degraded by cholinesterase enzyme Same chemicals are inhibitors of cholinesterase Ex- Sarin gas, Novichok agent = block cholinesterase, acetylcholine last longer in body à skeletal muscle stays contracted and can’t relax muscle à slow heart rate, can’t breathe well Biogenic Amines o Small, charged molecules synthesized from amino acids  § Dopamine: movement, learning, attention, reward and addiction § Norepinephrine: alertness, mood § Serotonin: mood, sleep, hunger, digestion § Histamine: allergic reactions, stomach acid production, brain activity Structure of the Nervous System Peripheral o A?erent division § Somatic sensory § Visceral sensory § Special sensory o E?erent division § Somatic motor § Autonomic motor Regulates a lot of involuntary functions o Sympathetic o Parasympathetic o Enteric Controls function of majority of organ systems Autonomic Nervous System Same organ innervated by both sympathetic and parasympathetic o Organ is innervated by a neuron: neuron has a synapse with that organ, usually with smooth muscle in te organ or an endocrine or exocrine gland o It will have opposing e?ects on that organ o Sympathetic (SNS) § “Fight or flight” § NT: norepinephrine § Dilates pupils, bronchioles, vessels increases heart rate inhibits digestion o Parasympathetic (PSNS) § “Rest and digest” § NT: acetylcholine § Constricts pupils, bronchioles, vessels decreases heart rate stimulation digestion o Enteric (ENS) § Controls motility, secretion, sensation of GI tract (sense when full, need to go to bathroom etc.) § Contains sensory and motor neurons and interneurons § = your gut’s “brain” Contains both a?erent and e?erent Work on its own without too much input from CNS because most activity controlled by sympathetic and parasympathetic nervous system which are part of peripheral nervous system The enteric nervous system uses the same type of neurotransmitters as the central nervous system (mostly serotonin). Some gastrointestinal disorders such as irritable bowel syndrome, which is often characterized by hypersensitivity and increased motility of the digestive tract, can be treated with low levels of the same antidepressants used to treat depression (serotonin reuptake inhibitors, which increased the amount of time that serotonin sits around in synapses after being released. Topic 09: Sensory Physiology Sensory system Two components: o Sensory receptors: receive stimuli from external or internal environment = specialized cells o A?erent neural pathways: conduct information from receptors to CNS (involve interneurons) = chains of neurons § Sensory: a?erent; motor: e?erent § E?erent neural pathways: convey information from brain to muscles (or endocrine gland) in order to move body part (or secrete hormone) We are not aware of all sensory stimuli o Sensation: sensory information that reaches (cerebral cortex) consciousness o Perception: awareness of sensation or understanding of its meaning § Ex- pain: sensation, perception: awareness that a tooth hurts Sensory Receptors It is specialized sensory cells that respond to sensory stimuli Types: o Mechanoreceptors § For touch, hearing, balance § Mechanically-gated ion channels used to open and produce graded potential o Thermoreceptors § For temperature § In skin o Photoreceptors § For light (vision) Receive light for vision o Chemoreceptors § For chemicals (taste, smell) § Ligand-gated ion channels o Nociceptors § For pain Stimulus: energy (light, sound, etc.) or chemical that activates receptor Sensory transduction: transformation of environmental stimuli to electrical stimuli (neural response) Sensory Transduction Stimulus causes opening or closing of ion channels in sensory receptors, which produces: o A graded potential (receptor potential) § Chemoreceptor: stimulus binds to structure à gate opened à ions flow in/out of cell § Mechanoreceptor: physical deformation of membrane (membrane stretched in both direction) à ion channel opened § Photoreceptor: specialized protein inside photoreceptor à protein hit by light à open/closing of ion channels In some specialized sensory receptors (eg. like ones in the eye), a graded potential is enough to trigger NT release onto an a?erent neuron o They don’t undergo APs; stimulus causes graded potential su?icient to cause NT release o A?erent neuron will have action potential à transmit message to CNS Stimulation of Sensory Receptors Information is conveyed by 2 characteristics of resulting signals: o Magnitude of grade potential (green graph) § Stronger stimulus greater receptor potential vice versa (orange graph) Stronger stimulus cause larger graded/receptor potential because it triggers more ion channels (usually Na+) to open à more positive ions flow into the cell à depolarization occurs o Frequency of action potential § Weaker stimulus depolarizes the cell enough to hit threshold à action potential Less frequent action potential à less NT released § Stronger stimulus causes the cell to be depolarized even more à high above threshold à more frequent action potential More frequent action potential à a lor more NT released o Summary § Stronger stimulus à larger graded/receptor potential à more frequent action potentials at axon where voltage- gated Na+/K+ channels are present à at axon terminal more neurotransmitter released Important characteristics of stimuli are: stimulus type, stimulus intensity, stimulus location Stimulus Type Each sensory neuron responds to stimuli within its receptive field o Receptive field: area or volume of the body monitored by a sensory neuron § Each neuron has a receptive field  Modality: stimulus type o Ex- temperature, taste, touch, vision, etc. Submodality: specific category within modality o Ex- hot/cold, sweet/salty/sour, etc. § Purple and blue cell respond to temperature as stimulus but the two are for di?erent types of temperature § Submodality for vision could be color, brightness, size of visual objects, etc. Most receptors are specialized for one modality or submodality but can overlap (esp. when stimulus is very strong) o Ex- sensory cells in the eye will respond to light but not to sound o If stimuli are very strong à can trigger a number of receptors § Ex- close your eyes and rub eyes with knuckles à see stars Feeling both pressure and seeing § Ex- extremes of heat can come with pain Stimulus Intensity How do we distinguish a strong stimulus from a weak one? o Increased frequency of APs from one receptor in an area § Weak stimulus à cause opening of mechanically gated ion channel in few of sensory nerve endings à some frequency of action potential § Strong stimulus à hit all nerve endings à more mechanically gated ion channels open à more depolarization, larger graded potential, more frequent action potential o Increased number of receptors stimulated (stronger stimuli a?ect larger area of body) Stimulus Location How do we determine the location of a stimulus? o Specific a?erent pathways (chains of specific neurons) by which information travels to CNS o Specific location in CNS that are associated only with that modality Acuity: precision with which we distinguish multiple stimuli (tell them apart) o Depends on: § Size of receptive field: smaller receptive field = higher acuity § Amount of convergence of a?erent pathways Do sensory neurons that perceive di?erent stimuli all synapse on the same interneurons o Less convergence = better acuity Improving Acuity: Size of Receptive Fields Large receptive field o Apply stimulus with two separate points à hit receptive field of same neuron à can’t distinguish one from the other because same neuron receiving both stimuli Small receptive field o Apply stimulus with two points à each two points will hit receptive field or di?erent sensory neuron à perceive as two separate points o Can better distinguish 2 separate stimuli o Can pack more receptors in one area o Used in more sensitive areas of body § Ex- sensory neurons in retina of eyes Improving Acuity: Overlapping Receptive Fields B= receptive fields overlap with A and C Applying stimulus in the middle of B o Overlapping receptive fields help localize exact location of stimulus o Ex- center of receptive field of B Applying stimulus in the middle of A and B Ascending Sensory Pathways Ascending pathways: a?erent sensory pathways (ascending up spinal cord to brain) Specific vs. nonspecific pathways o Specific: separate pathways for each modality § Make synapse with di?erent interneurons; two separate lines of communication § Into from touch and temperature arrive in two separate places in cortex and be perceived as two separate sensations o Nonspecific: information about several modalities converges on same pathway § Touch and temperature information synapse on the same interneurons and go to same area of cerebral cortex; can’t distinguish between the two o Specific ascending pathways give better acuity Descending Sensory Pathways Descending pathways: signals coming from brain to periphery (descending down the spinal cord form brain) o Usually used to refer to e?erent (motor) pathways o In some cases descending pathways can be used to modify a?erent pathways § Depolarized à release NT on ascending interneurons, depolarized à information flows to next neuron up to the brain § Descending information starting in brain leads to inhibitory interneurons à release NT on the same a?erent neuron that the sensory neuron released its NT on à cancel out and neuron doesn’t pass information from sensory brain up toward brain Inhibitory interneuron in the descending pathway would prevent an action potential in the a?erent neuron by opening ligand-fated K+ channels in the a?erent neuron o Inhibitory NT released by inhibitory neurons cause hyperpolarization by opening ligand-gated K+ channels and causing K+ to flow out of the cell o Can inhibit ascending pathways and alter sensation and perception § Ex- brain can decrease or modify perception of pain  Ex- bear chasing you à pull a muscle in hamstring à running away more important than hamstring à still be getting the stimulus; triggering sensory neuron, but descending information sent down to inhibit pain message à pain message doesn’t get to the brain à don’t sense the pain during fight or flight Sensory Areas of the Cortex Ascending pathways first pass to spinal cord and brainstem Then to specific areas of cerebral cortex o Somatosensory cortex (touch) o Visual cortex (vision) o Olfactory cortex (smell) o Gustatory cortex (taste) o Vestibular cortex (balance) Then processed by cortical association areas which process and integrate sensory information o Processing involves attention, learning, memory, language, emotion, experience o Can be altered by illness, drugs, etc. § Ex- less sensitive to sensations when you’re tired, feeling more pain when upset, learning to taste something bitter like co?ee, taste of food being a?ected by the memory of growing up eating it, etc. General and Special Senses General senses o Somatic sensation: from skin, muscles, tendons, bones o Visceral sensation: from internal organs (usually has few receptors) o Receptors respond to: § Touch and pressure: sensed by mechanoreceptors § Posture and movement § Temperature: sensed by chemoreceptors § Pain: sensed by mechanoreceptors Special senses o Vision o Hearing o Equilibrium/balance o Taste o Smell Touch and Pressure Many types of mechanoreceptors Respond to: o Touch o Pressure o Vibrations o Hair bending Many are highly specialized o Neuron ending are within collagen containing capsule Receptor fields vary: o Small: provide precise information o Large: provide information about skin stretch or joint movement Mechanically-gated ion channels and voltage-gated ion channels would be present in mechanoreceptors o Receptors respond to mechanical stimuli à open mechanically-fated ion channels and cause graded potential o Voltage-gated ion channels for action potentials and releasing neurotransmitter onto other neurons in the a?erent pathway in order for information about stimuli to reach the brain Posture and Movement Mechanoreceptors in muscles, joints, tendons, ligaments, skin o Muscle spindle stretch receptors o Sensory stimulus when muscle pulled in one direction o Golgi tendon organ: detect stretch  Sense muscle stretching and prevent overextension Enable muscle groups to work in opposition o Kick leg out à quadriceps contract, hamstring elongates o Kick leg back à quadriceps elongated, hamstring contact o If quadriceps contracts and shortens, while hamstring relaxes and elongates; hamstring muscle spindle stretch receptors will have a higher frequency of action potentials during a leg rise § When quadriceps muscle contracts, it shortens à reduces stimulus for the quadriceps spindle stretch receptors and trigger no action potentials § When hamstring muscle relaxes, it elongates à increases spindle stretch hamstring spindle stretch receptors and trigger action potentials in response Sense of movement: kinesthesia Sense of posture: proprioception Vision and vestibular systems (regulate equilibrium) also play a role in posture and movement Temperature Thermoreceptors with free axon terminals, usually not myelinated Temperature sensors are ion channels in axon terminals o Transient receptor potential (TRP) proteins o Various TRPs open at a range of temperatures o Can also open in response to ligands § Ex- chili (capsaicin) à makes you feel warm, menthol = mint gives you cooling sensation Menthol: binds to and opens TRPA1 ion channel o TRPA1 is the only channel that opens at colder temperatures à gives sensation of cold Pain Sensed by nociceptors o Stimulated by: extreme pressure, temperature, or irritating chemicals made by immune cells o Usually signals: cell/tissue damage o Brain can modify perception via descending pathways § A) Nociceptor impulse reaching axon terminal of nociceptor neurons à release substance P à binds to receptor § B) Descending neurons produce NT that bond to opiate receptor à hyperpolarize axon terminal of nociceptor à prevent from releasing NT on to the a?erent neurons that take information to the brain Produces natural “opiate” neurotransmitters such as endorphins and enkephalins o Natural and synthetic opiates block: § Transmission of signals from nociceptors to a?erent neurons § Receptors will stop transmitting information in response to these opiates Visceral Sensation Brain doesn’t distinguish stimuli coming from visceral and somatic branched of the same spinal nerve due to: o Convergence of visceral and somatic sensory neurons on the same a?erent pathways Feel pain from an internal organ as another area of the surface of the body, which is called: referred pain  o Referred pain § Ex- undergoing heart attack à heart sensing painful stimulus caused by loss of blood flow to cardiac muscle à cardiac muscle dies Intense pain on the left side of your chest and inside of left arm because sensory neurons that innervate the skin in this region makes a synapse with the same interneuron as the sensory neurons that innervate heart Ex- issues with liver and gallbladder felt in upper abdomen but due to referred pain, it can also be felt on the right side of the neck Ex- pain in lower abdomen and lower back that radiates down the thighs would suggest issue with kidneys Somatosensory Cortex A?erent pathways for general senses end at the somatosensory cortex Sensations from di?erent body parts perceived by di?erent regions of the cortex Area of cortex dedicated to a body part is proportional to the density of sensory receptors in that body part: sensitivity/acuity (map is =somatosensory homunculus) o Coming from general senses like touch of facial area = take up larger area than for sensations coming from legs Topic 09-2: Special Senses Vision Humans can sense a small part of electromagnetic spectrum o Di?erent wavelengths = perceived as di?erent colors Eye detect light and wave o Optical component = lens (part of the eye that focuses light) § Focuses visual image onto the receptor cells o Neural component = retina § Transform image into pattern of graded and action potentials Light is focused on a photoreceptor o Light energy changes the shape of a molecule in photoreceptor à triggers signaling pathway that alters photoreceptor’s permeability to ions à create graded potentials that can be used to release NT and trigger AP in other a?erent neurons Photoreceptors Light passes through cornea à lens -à retina Photoreceptors are located in the back of the retina o Rods: perceive “white light” in middle spectrum § Extremely sensitive, work well in low-light conditions o Cones: perceive di?erent colors (2 di?erent cones) § Work best in bright conditions  Contain photopigments that absorb light o In rod: rhodopsin o In cones: 3 di?erent photopigments Photopigments contains: o Retinal: small molecule that changes conformation when hit by light o Opsin: protein that is bound to retinal o Each opsin binds in di?erent way to retinal making it more sensitive to a di?erent portion of the spectrum Retinal changes conformation in response to light o Alters how opsin protein interacts with other proteins in photoreceptor Phototransduction At rest (no light), the cell is relatively depolarized (-35mV) à opposite from most neurons In response to light, it hyperpolarizes (-70mV) o Usually -70mV at rest, voltage increase, depolarize in response to stimulus Depolarizes due to opening of ligand-gated Na+ and Ca2+ channels Ligand: cyclic GMP (cGMP) o Similar to cAMP Guanylyl cyclase produces cGMP (GTP à cGMP) o In presence of cGMP, ion channels open o More active in dark because it produces cGMP à when it binds to and opens Na+/Ca2+ channels à positive ions move into the cell and depolarize it § In the dark, there must be a lot of cGMP, more active guanylyl cyclase cGMP phosphodiesterase (PDE) o Degrades cGMP to regular GMP o In absence of cGMP, channels close When hit by light, retinal changes shape à activates rhodopsin protein Rhodopsin activates transducing Transducing activates cGMP phosphodiesterase (PDE) = ligand for opening of ion channel Result: degrade cGMP à ion channel close à hyperpolarize In the dark:  o Guanylyl cyclase is active o Makes cGMP o Ion channels open o Cell is depolarized In the presence of light: o Rhodopsin is activated o Transducing is activated o PDE is activated o Degrades cGMP o Ion channels close o Cell is hyperpolarized Neural Pathway for Vision Signals are passed from photoreceptors à bipolar cells à ganglion cells à visual cortex Photoreceptors & bipolar cells have no voltage-gated channels o Type of potentials (graded potentials): § Voltage-gated channels are required for action potentials à only graded potentials § Cells are small so graded potential enough to send message Bipolar cells can spontaneously depolarize and release NT in absence of other signals o Have a lot of leak channels à spontaneously depolarize à release NT to ganglion cells Ganglion cells are the first in the pathway that have voltage-gated channels o Type of potentials (action potential and graded potentials): § Ligand-gated ion channels that bind to NT released by bipolar cells à graded potential § Voltage-gated channel present à action potential For ganglion cells that have very long axons that carry information long distances from the retina to the cerebral cortex In the dark: o Rods: depolarized à release glutamate NT onto bipolar cell o Bipolar cells: § Hyperpolarize in response to glutamate à do not release NT onto ganglion cell Hyperpolarized: positive ions move out of the cell or negative ions coming in Cl- channel opened à negative ion comes in à voltage becomes more negative = hyperpolarization o Na+/K+ pump à intracellular Na+ and Ca2+ concentrations are low à Na+, K+ flow into the cell à depolarizing Ligand-gated Cl- channel opened by glutamate o Ganglion cells: § Not depolarized à no AP § Brain doesn’t receive information In the presence of light o Rods: hyperpolarized à glutamate not released from the rod § Do not release glutamate o Bipolar cells: depolarize in absence of glutamate à NT released onto ganglion cell o Ganglion cells: depolarize à can trigger AP à brain receives information What type of NT is glutamate? o Inhibitory § Probably binds to either K+ or Cl- channels à cause positive ions to leave cell if it’s K+ or negative ions to come into cell if it’s Cl- à either case causes it to hyperpolarize à prevents it from releasing NT What type of NT do bipolar cells release? o Excitatory § Probably opens Na+ or Ca2+ channels in ganglion cell à depolarize à trigger AP Binocular Vision Axons of ganglion cell form the optic nerve 2 optic nerves meet at the optic chiasm in the brain where some fibers cross o Some visual information from left eye goes to right side of visual cortex and vice versa A?erent pathway ends at the visual cortex Advantage of binocular vision o Enables depth perception or the ability to accurately gauge distances of object from you Sound Sound caused by energy transferred through a medium (gas, liquid, or solid) causes the molecules to vibrate o Sound can’t occur in vacuum(no medium) Sound Waves Loudness o Determined by wave’s amplitude (height of wave) § Measured in decibels (log scale) Pitch o Determined by wave’s frequency (width of wave or waves/sec) § Measured in hertz (Hz; cycles/sec) o Deeper pitch à wider width Sound Transmission Step 1: o Sound is collected and funneled into ear canal by pinna (external ear) o Sound enters external auditory canal o Causes tympanic membrane (eardrum) to vibrate Step 2: o Tympanic membrane is connected to bones of the middle ear (ossicles) § Bonds help amplify vibrations à fluid the cochlea starts moving o Vibration of tympanic membrane causes ossicles to vibrate o Ossicles are attached to oval window, or a membrane at the entrance to the cochlea § Basilar membrane: contains sensory receptors § Cochlea: filled with fluid; fluid compressed and vibrates when stapes pushes against it à membrane moves as a result Spiral-shaped, fluid-filled space within in temporal bone Contains several membranes that divide cochlea lengthwise into separate sections Step 3: o Vibrations of oval window causes fluid in cochlea to vibrate o Basilar membrane vibrates § Cause hair cells to move à change in graded potential à NT released form sensory cells to a?erent neurons (yellow) § Hair cells have mechanically-gated ion channels (stimulus: mechanical movement of sensory cells against membranes)  Sensory receptors of the inner ear: hair cells Located within the Organ of Corti, which sits on the basilar membrane Hair cells have movable “hair” at one end called stereocilia (attached to tectorial membrane) These are embedded in an overlaying membrane called: tectorial membrane Basilar membrane (moves in response to sound) vibrates and tectorial membrane stays still à hair cells moved against tectorial membrane Auditory Signal transduction Step 4: o Basilar membrane moves in response to sound o Pulls stereocilia against tectorial membrane & cause them to bend o result: stereocilia bent in a particular direction, proteins connecting each individual stereocilia opens mechanically-gated ion channel à cause cell to depolarize à graded potential releases NT on to the a?erent neurons à APs in a?erent neurons § (b) stereocilia bends in one direction ion channel opens (c) but if bends in the other direction, ion channel closes § Always bent in longer direction Video Sound enters ear à external auditory canal à tympanic membrane vibrates in response to sound o Lower pitch sound = slower rate of vibration o Lower volume = less dramatic vibration o Higher frequency sound = faster vibrations Tympanic membrane vibrates ossicles passing on the information of frequency and amplitude o Tympanic membrane articulates with auditory ossicles (3 bones) Vibrations are transferred to footplate of stapes Stapes moves with piston-like action, sending vibrations to “bond labyrinth” o Labyrinth filled with perilymph (fluid) Vibrations produced by stapes are drawn into cochlea and return to meet round window Cochlear duct filled with endolymph o Cut in cross section § Reissner’s membrane and basilar membrane move in response to vibrations traveling up the scala vestibuli § Movements of the membranes then send vibrations back down to scala tympani Organ of corti on basilar membrane o Hair cells in organ of corti sends nerve impulses to the brain via cochlear nerve o Hair cells are covered by tectorial membrane o As basilar membrane vibrates, hair cells are bent against the tectorial membrane à trigger hair cells to fire o Specific area long the basilar membrane move variably in response to di?erent frequency of sounds § Lower frequency: vibrations closer to apex § Higher frequency: vibrations closer to base Auditory Signal Transduction Distinguishing amplitude o Louder sounds cause stronger vibrations o Hair cells have larger or longer graded potentials o Release more NT onto a?erent neuron § Loud sound à stronger vibrations à more mechanically-gated ion channels to open in hair cells à larger graded potential and more NT à increased frequency of action potentials in a?erent neurons o Frequency of action potentials in a?erent neurons tell brain whether stimulus is mild or strong Distinguish pitch  o Basilar membrane more narrower and sti? close to oval window à becomes wider and more floppy towards other end § Primarily a?ect hair cells closer to the oval window but not hair cells that are at the other end of the basilar membrane o Di?erent frequencies will vibrate di?erent places along the basilar membrane § Lower frequency à depolarization near helicotrema basilar membrane § Higher frequency à depolarization near oval window basilar membrane o A?erent pathways end at the auditory cortex Vestibular System Made of interconnected, membrane-covered, fluid-filled tubes Vestibular information is used to: o Control eye movement o Maintain posture and balance o Provide awareness of body position and acceleration § Aside from vestibular system, vision, proprioception, kinesthesia à provide awareness of body positioning and movement in space Components: o 3 semicircular canals: detect rotation of head o Utricle: detects horizontal acceleration o Saccule: detects vertical acceleration Type of receptors: o Mechanoreceptors (hair cells) Semicircular Canals Detect rotation of the had along 3 axes: o “yes” o “no” o Ear to shoulder Receptors are hair cells located in the ampulla o Rounded bulge in the canal o Stereocilia are embedded in cupula (gelatinous substance) Head movement causes fluid inside canal to move due to gravity o Fluid pushes on cupula o Stereocilia are moved § Toward tallest stereocilia à open ion channel § Toward shortest stereocilia à closed ion channel Rotate head à fluid inside semicircular canal with move with respect to gravity à exert pressure to cupula inside the ampulla à cause stereocilia to bend and hair cells to depolarize à release NT onto a?erent neurons à take information to vestibular cortex of the brain Hair cells of the Semicircular Canals Ion channels open when stereocilia are bent on way but not another o Move head in one direction à mechanically-gated ion channels open à sensory neurons depolarized à more NT released and cause higher frequency of action potentials in a?erent neurons (right ear towards right shoulder) o Move head opposite direction à mechanically-gated ion channels close à hyperpolarize due to leak channels and Na+/K+ pump à frequency of AP decrease (left ear toward left shoulder) Causes graded potential à release NT onto a?erent neuron -> APs in a?erent neuron A?erent pathways end at the vestibular cortex Utricle & Saccule Provide information about linear acceleration o Head moving up & down and back & forth  o Hair cells are covered by a layer of gel and calcium carbonate crystals called otoliths Utricle o Hair cells respond to horizontal accelerations Saccule o Hair cells respond to vertical accelerations Acceleration causes otoliths and gel to move in one direction due to gravity o Hair cells synapsing with a?erent neurons o Body at rest or constant motion: cells depolarize a little bit, some NT release, frequency of AP low o Forward acceleration: move structure of head forward, base of the cell moving faster than gel and otolith, stereocilia will be bent by heavy liquid à increase frequency of AP, tell brain you’re accelerating forward o Backward acceleration: base of the cell will move in backward direction, stereocilia bent toward shortest one, no ion channel opened, frequency of AP decreases Pulls stereocilia of hair cells in one direction Causes: graded potential à release NT into a?erent neuron à APs in a?erent neuron A?erent pathways end at the vestibular cortex Taste (gustation) Taste buds are found in the walls of the lingual papillae Basic types of taste receptors: o Sweet o Sour o Salty o Bitter o Savory (umami) Gustatory Transduction Ligands: o Sweet: monosaccharide and disaccharides o Salty: Na+ o Sour: H+ o Umami: glutamate o Bitter: plant alkaloids (some toxic some not à have a lot of receptors for bitter taste) General pathway: o Ligand binds to receptor o Response: § Ion channels open or closed à cell depolarize à open voltage gated calcium channel à depolarization à released NT onto a?erent neuron à APs in a?erent neuron o A?erent pathway ends at the gustatory cortex Smell (olfaction) Olfactory receptor neurons lie in the upper part of the nasal cavity in the: o Olfactory epithelium: have cilia à increase surface area Odorants must pass through air and dissolve into mucus layer to be detected Odorants bind to: G protein-coupled receptors à intracellular pathway causes ion channels to open Olfactory Transduction Opening Na+ channel causes: o Depolarization à release NT onto a?erent neuron à APs in a?erent neuron A?erent pathway ends at the olfactory cortex