High Yield Physiology Remediation PDF

 Physiology Remediation: High Yield from Each Lecture (1-66) 1: Principles of Cell and Membrane Function (Benmerzouga)     The Cell:  Covered by plasma membrane (separates intracellular vs extracellular; important in creating and maintaining electrochemical gradients)  Cytoskeleton: to...

 Physiology Remediation: High Yield from Each Lecture (1-66) 1: Principles of Cell and Membrane Function (Benmerzouga)     The Cell:  Covered by plasma membrane (separates intracellular vs extracellular; important in creating and maintaining electrochemical gradients)  Cytoskeleton: to maintain and support the cells structure and function  Microfilaments: actin (smallest)  Intermediate filaments: (Keratin: epithelium) (Desmin: muscle) (Vimentin: connective tissue)  Glial fibrillary acidic protein: Neuroglial cells; Neurofilaments: Neurons  Microtubules: tubulin (largest)  Nucleus: DNA/Gene Regulation; Double-layered Membrane  NLS: can enter; NES: can exit  Nucleolus: makes rRNA  ER and Golgi:  RER: Proteins (ribosomes)  SER: Steroids, fats, phospholipids  Golgi → receives proteins on CIS side → modification → proteins exit on TRANS side  Mitochondria: Powerhouse of cell (ATP); has own DNA; susceptible to disease due to no DNA proofreading Plasma Membrane:  Phospholipids: Hydrophilic head; 2 hydrophobic tails (FAs)  Create bilayer (unsaturated have kink)  Cholesterol: Membrane rigidity and stiffening Transmembrane Proteins:  G-Protein Coupled: Signaling cascade: Adrenergic and muscarinic receptors (neuronal pathways)  Ligand Binding Receptors: Requires something to bind to open the channel (i.e. insulin)  Adhesion Molecules:  Integrins: Cell matrix adhering molecules  Cadherins: Cell to cell adhesion molecules Movement Across the Membrane:  Large, uncharged, polar: transporter  Small, uncharged: more or less freely move  Hydrophobic: can diffuse across  Ions → Channel  Voltage Gated: Charge open  Ligand Gated: Ligand binds to open  Mechanically Gated: Stretch or pressure opens  4: Membrane Transport (Benmerzouga)  2 and 3: Resting Membrane and Action Potential I and II (Benmerzouga)     Electrochemical Gradient:  INSIDE: negative; OUTSIDE: positive  Na+ mostly outside  K+ mostly inside  Distribution of ions across the membrane leads to a polarized cell with a NEGATIVE resting membrane potential  Membrane potential = E net = E in - E out  Normal resting membrane potential is -60 mV  When an ion reaches equilibrium between the inside and outside, its movement stops and this point is called the Electrochemical Equilibrium. (This point is never really reached b/c other ions are present and therefore it is theoretical)  Equilibrium points of ions are determined by the Nernst Equation Driving Force:  Na+ is mostly outside the cell so the concentration gradient pulls Na+ in the cell. Na+ is positively charged and the inside of the cell is negative so the electrical gradient pulls Na+ in the cell as well.  Since both are pulling Na+ into the cell, Na+ has a LARGE driving force into the cell. (Na+ is the ion involved in depolarization of the cell so it makes sense that its driving force would be large.)  K+ is mostly inside the cell so the concentration gradient pulls K+ out of the cell but K+ is positively charged and the inside of the cell is negatively charged so the electrical gradient pulls K+ in the cell.  The gradients are in opposite directions and therefore K+ has a SMALL driving force.  Cl- has a SMALL driving force  Ca+ has a LARGE driving force (cardiac myocyte depolarization) Excitement of Cells:  Depolarization: Cell becomes more positive (Na+ influx)  Repolarization: Cell becomes more negative again (K+ efflux)  Hyperpolarization: Cell becomes more negative, past resting potential (K+ efflux) Clinical Correlations: Hyperkalemia (too much K+ outside of cell): increases resting membrane potential leading to partially depolarized state  Hypokalemia (too little K+ outside of cell): leads to hyperpolarization of the cell Nerve Conduction:  Neurons live at their resting membrane potential, which is maintained by the Na+/K+ ATPase (3Na out, 2K in)  That membrane potential is NEGATIVE, and is about -55mV.  When a neuron is stimulated to the point it reaches threshold, Na channels open -> Na influx and depolarization occurs: Depolarization is ALL OR NOTHING  Timed summation: one neuron sending small stimulatory signals in rapid succession, to the point the postsynaptic neuron reaches threshold  Spatial Summation: Multiple neurons sending small stimulatory signals to one postsynaptic neuron, bringing it to threshold  Note: Not all neurotransmitters are stimulatory, some are inhibitory (example GABA). In spatial summation the stimulation must outweigh the inhibition to reach threshold.  Once threshold is reached, Na+ channels open, leading to influx  Rising Phase: Positive charges rush into the cell, bringing the overall charge of the cell closer to 0  Overshoot Phase: Na influx is so fast that the membrane potential rises past 0, to about +25  Depolarization Peak: Voltage Gated K+ Channels open leading to a K+ EFFLUX  Repolarization: positively charged K leaves the cell, bringing membrane potential back towards normal resting, more K+ exits than needed, causing after hyperpolarization  Refractory Periods:  If all channels have their inactivation gates closed, there is no possibility for an action potential, this is the absolute refractory period  If some channels have their inactivation gate closed, while others have it open, an action potential could potentially be sent. This is the relative refractory period, and there is a higher likelihood of reaching threshold if more Na channels have their inactivation gates open.  Action Potentials travel via active propagation.  There is constant velocity, and constant amplitude (the signal is as strong at the end of the tract as it is at the start).  Active propagations have high amplitude and the ability to depolarize the next neuron in the tract.  Graded potentials are stimuli that don’t bring the neuron to threshold, they travel down the axon but they fizzle out over distance.    Types of Transport  Passive: simple (without help) or facilitated (with help of a carrier protein/channel); solute moving from high concentration to low concentration, requiring NO ENERGY  Active transport can be primary or secondary, but always low concentration to high concentration  Primary: ATP is directly broken down to bring molecules against their gradient(Na+/K+ ATPase)  Secondary: Utilizes the ion gradient made by an ATPase, pairing the transport of one molecule down its gradient with the transport of another molecule against its gradient (Na+/Glucose symporter) Transport Rate: Mediated by membrane thickness, area, Fick’s Law (membrane permeability x concentration gradient), size and polarity of molecule  i.e. A small, nonpolar molecule with a large concentration gradient will diffuse across a large thin membrane the fastest  Limited by the number of proteins available.  Carrier proteins have a maximal rate of transport (Vmax). Once Vmax is reached, increases in concentration gradient will not affect transport.  When carrier proteins are at Vmax, they are saturated Types of Transport Proteins  Membrane Pores: have a range of selectivity based on lumen size and lumen amino acid profile  Gated Ion Channels: open/close based off either membrane potential, ligand binding(Ach binding nicotinic channels), or secondary messenger(cGMP mediated Na+ channel)  Carriers: molecule binds extracellularly, inducing a confirmation change, and is released intracellularly (GLUTs, Urea Transporter, Organic Cation Transporter)  Pumps and ATPases for primary active transport (Na+/K+ ATPase, Ca Pump, H+ pump)  Symporters and Antiporters for secondary active transport (SGLT, cotransporters, and exchangers Non-Protein Transport Routes  Vesicular:  Endocytosis: Uptake of extracellular particles where plasma membrane is pinched off to surround particles in a vesicle  Exocytosis: Release of particles into extracellular environment, vesicle fuses with the plasma membrane  Phagocytosis: Ingestion of large extracellular particle, specific to immune cells such as macrophages  Pinocytosis: endocytosis of fluid    Bulk flow:  Seen in capillary beds, bulk flow is the movement of nutrients from blood to cells, and waste from cells to blood.  It is mediated by the balance between hydrostatic and osmotic pressure gradients; happens across endothelium Clinical Correlations  Diarrhea: the intestines are lined by epithelial cells bound together by tight junctions. Some bacteria secrete enterotoxins that increase cAMP, and bind apical membrane proteins to release ions into intestinal lumen. Water will follow the osmotic pull of the solutes, increasing water content in the lumen, giving the symptom of diarrhea.  Cystic Fibrosis: defect in the CFTR channel, no Cl- transport into the lumen of respiratory, GI, GU tracts. Water follows ions, when Chloride ions aren’t pumped into the lumen, osmosis won’t occur to thin secretions of exocrine glands. Net result is very thick mucus prone to infection. Epithelial Cells: the barrier between the internal and external environment  Apical membrane = lumen side = external side  Basolateral membrane = connective tissue side = internal side 5: Body Fluids, Osmosis, and Tonicity (Benmerzouga)                    Osmolarity: the concentration of osmotically active particles per liter of solution Osmosis: the flow of water between two solutions separated by a semipermeable membrane Osmotic pressure: the driving force for osmosis is caused by the presence of a solute Osmolality: a measure of the number of osmotically active particles per kilogram of H2O Tonicity: the effect of a solution on a cell Reflection coefficient (σ): The extent to which a particular solute crosses a particular membrane is expressed by a dimensionless factor called the Osmotic coefficient: (g): The number of particles that a solute dissociates to Steady state is when the intracellular and extracellular osmolarities are equal, there is no osmotic pull in a particular direction, no volume fluctuations, and water into the cell=water out; reached between the range of 280-295mOsm/kgH20 60% of total body weight is water (50% in women) 40% of total body weight is intracellular water 20% of total body weight is extracellular water  25 % of extracellular fluid is plasma, the other 75% is interstitium Starling forces mediate the flow of extracellular water via hydrostatic and oncotic pressure gradients The type of capillary in the system alters extracellular water transit. In order from lowest to highest permeability: continuous, fenestrated, sinusoidal (discontinuous) Tonicity is how osmolarity affects cell volume, does the cell stay the same, shrivel up(lose volume), or swell(increase in volume) as it sits in a solution Isotonic: intracellular and extracellular osmolarities match Hypertonic: high extracellular osmolarity, water efflux from the cell causing it to lose volume and shrivel Hypotonic: low extracellular osmolarity, water influx into cell causing swelling and potential lysis remember: hippotonic Tonicity is depended on the effective osmoles, the molecules that do not regularly cross membranes by themselves. O2 is an ineffective osmole, ions are effective osmoles, as well as proteins like albumin. Calculations  Osmolarity= osmotic coefficient x concentration units(mOsm/L)  Find relative tonicity by comparing multiple osmolarities, ask what has more solutes and where will water go if these solutions were next to each other with a semipermeable membrane  Effective osmotic pressure= reflection coefficient x osmotic coefficient x concentration x .0245 units (atm) Isosmotic Volume Changes:  Contraction: example sweating or diarrhea; No change in osmolarity, the only thing that changes is extracellular volume decreases    Expansion: example SIADH(inappropriate increase in ADH release, water reabsorption no salt reabsorption); Increase water content extracellularly, water shifts extracellular—>intracellular to balance osmolarity 6: Physiology Applications (Benmerzouga)  Clinical Applications  Remember when solving volume shift problems, osmotic pressure is the pulling force solutes have on water, and water flows either intracellularly or extracellularly until osmolarities are balanced  Total body water(estimate)=.6 x Body weight(males) or .5 x Body weight (females)  Today body water(exact)={[labeled injected]-[labeled excreted]}/[labeled plasma]  Total body water=ICF+ECF  Plasma osmolarity estimates= 2Na, or 2Na+glucose/18 +BUN/2.8 7: Neurophysiology I (Benmerzouga)      Expansion: example IV normal saline(0.9%); No change is osmolarity, the only thing that changes is extracellular volume increases   Hyperosmotic Volume Changes:  Contraction: Excessive heat with no water replacement, dehydration; Loss of extracellular water, leaving high solute concentration outside cell, water shifts intracellular —> extracellular to balance osmolarity Hypoosmotic Volume Changes  Contraction: hypovolemic hyponatremia, example is adrenal insufficiency(no aldosterone); Loss of solutes extracellularly, osmotic pull shifts water extracellular—>intracellular to balance    Expansion: high salt ingestion; Increase in extracellular solutes, bringing extracellular osmolarity up, water shifts intracellular —> extracellular to balance osmolarity  Glial Cells  Microglia: Immune system of the CNS  Oligodendrocytes: Form and place myelin on CNS neurons  Astrocytes: Support functions, most notably they help form the BBB Schwann Cells: Form and place myelin on PNS neurons Ependymal Cells: Line ventricles of CNS Conduction Velocity of Neurons (V=L/T) Myelin: Lipid insulator  Increases membrane resistance (channels are open, charge can flow easily --> High Conductance)  Decreases capacitance (how fast can the neuron respond to the charge flow)  Without myelin = longer, leakier, higher capacitance and slower conduction velocity speeds.  As a result, axons with myelin sheaths depolarize faster and transmit signals faster  Some neurons are unable to conduct an AP if the axon is severely demyelinated Diameter  Conduction velocity of myelinated axons increases linearly with diameter Thinnest = C fibers (all unmyelinated b/c diameter is so small they don’t need myelin although they are still the slowest and conduct chronic pain signals) Thickest = ALL are myelinated if larger than 1 um!! Carry quick sensory info (i.e., immediate pain from injury or muscle stretch) Length constant is inverse to the resistance of the axon  Length constant = 1/e = the distance that it takes the membrane potential to decrease to 37% of its starting value        As length increases, resistance decreases Increase in diameter is an example of increase in length therefore with increased diameter, the resistance decreases. Saltatory Conduction  The ability of the conduction current to “jump” between nodes of a myelinated axon Nerve Fibers:  Peripheral neurons are bundled together ---> a bundle of neurons is covered by the epineurium ---> this bundle covered by the epineurium is called a nerve.  A fibers:  large and heavily myelinated  Can be compressed --> loss of stimuli  Touch, proprioception, motor function and some pain  Include alpha, beta, gamma, and delta  B fibers:  Preganglionic of ANS  Small and lightly myelinated  C fibers:  Sympathetic from soma to periphery  Small and unmyelinated  Local anesthetics work here  Pain and temperature  Can still produce APs despite temperature decreases Guillain-Barre = loss of myelin sheath in the PNS usually following an infection  These neurons are capable of remyelinating ---> patients usually recover Multiple Sclerosis = loss of myelin in the CNS with an unknown cause  These neurons cannot remyelinate ---> patients never get better and treatment is aimed at slowing the disease progression Action Potential of Neurons  Happen in the same fashion as other cells (Depol = Na influx, repol = K outflux)  There are more Na+ channels at the initial segment (first part of axon) and the nodes of Ranvier than anywhere else  The threshold is lower in these regions and therefore it is easier to produce an AP (initial segment) or keep it going (nodes)  EPSP = excitatory neurotransmitter depolarizes the postsynaptic membrane  IPSP = inhibitory neurotransmitters hyperpolarize the postsynaptic membrane  Summation of EPSP (EPSP on their own don’t usually reach threshold for an AP)  Temporal = two EPSP that happen close in time sum together to create an AP  Usually the second EPSP is happening before the end of the first  Spatial = EPSP generated in synapses near each other can sum together to create an AP 8: Neurophysiology II (Benmerzouga)            Transmission types  Chemical Synapse  Neurotransmitters (NT) are released from neuron and bind a receptor  Named for direction of communication (axodendritic, axosomatic, axoaxonic)  Electrical Synapse  Current flows from one cell to another via gap junctions Steps in Neurotransmission (Chemical Synapse)  NT is made in neuron and stored in vesicles  AP causes depolarization down the neuron to the presynaptic nerve terminal  Voltage gated Ca channels are activated and open allowing Ca to enter the presynaptic terminal  Ca influx leads to vesicle fusion with plasma membrane and NT is released into synaptic cleft  NT binds ionotropic or metabotropic receptor  Signal is terminated by removal of NT from synaptic cleft  Enzymes can degrade NT in cleft  NT can be recycled into presynaptic terminal by reuptake  Ex: Glutamate is picked up by Glial cells or glutamate transporter and transferred back to neuron  Enzymes can also transmit signal Norepinephrine (NE) neurons in locus coeruleus Serotonin neurons in raphe nuclei; Hallucinogens Dopamine neurons in substantia nigra and ventral tegmental area; Parkinson’s Acetylcholine (Cholinergic) neurons in basal forebrain complex and project to hippocampus; also found in thalamus and forebrain NTs can be excitatory or inhibitory Excitatory depolarize membranes  Ex: Glutamate via ligand gated Na and Ca channels (direct) or Gq receptors (indirect) Inhibitory hyperpolarize membranes  Ex: GABA via ligand gated anion channels (direct) or Gi receptors (indirect) Potassium channels regulated by Ca or CAMP are more responsive to both excitatory and inhibitory currents Acetylcholine (ACh); Neuromuscular Junction (NMJ), presynaptic PNS and SNS and postsynaptic PNS; ALZHEIMER’S DISEASE     Amino Acid NT (Don’t get these confused, they all start with G); Glutamate: excitatory ---> prevents cell death (GlutaMATE is excited to be your mate :))  GABA: Inhibitory  Glycine: Inhibitory Biogenic Amines:  Catecholamines: Dopamine, NE, and Epi;  Monoamine: Serotonin ---> mood, appetite and nausea Peptides: Endocrine hormones, opioid, tachykinins Receptors  Receptor Types  Ionotropic = Fast  ligand gated channels that respond to NT in milliseconds  Metabotropic = slow  G-protein coupled channels that respond slow b/c they require a cased of signaling (cascades take time)  EPSP in the brain mediated by AMPA and NMDA channels  Both are Glutamate channels ----> excitatory ------> influx of positive ions ----> depolarization  AMPA is fast  NMDA is slow  NMDA allows Ca influx but at more negative Vm, Mg blocks the NMDA channel ----> harder to reach AP  IPSP in the brain are mediated by GABA  Implicated in a lot of drugs like barbiturates, phenobarbital, benzodiazepines 9: Sensory Receptors and Transduction (Benmerzouga)         Somatosensory System  Body’s state and interaction with the world connection with CNS  Sensory receptors transduce information about pressure, stretch, etc. that are processed into electrical signals called receptor potentials  Receptor potentials = is “graded” which means it may or may not be strong enough to generate an action potential Receptors  Mechanoreceptors = equilibrium, pressure, movement, vibrations  Ex: touch receptor = Pacinian corpuscle on skin  Thermoreceptors = cold and warm  Ex: cold and warm receptors on the skin  Nociceptors = pain  Ex: Polymodal or thermal nociceptors on the skin  Electromagnetic receptors = vision  Ex: Photoreceptors are rods and cones in the retina  Chemoreceptors = taste, smell, O2, CO2, osmolarity  Ex: pH of CSF in ventrolateral medulla Receptor Potentials  As receptor potentials rise above the threshold, the frequency of action potentials increase  As more branches of a nerve are stimulated, action potential frequency increases Adaptation  Fast adapting = Respond quickly but the action potentials do not continue despite continuous stimulus  Slow adapting = continue to produce action potentials until the stimulus ends Cutaneous Mechanoreceptors  Fastest = Pacinian (vibration, tapping)  Fast = Meissner and hair follicles  Slow = Ruffini, Merkel, and Tactile discs Neurons in Pathways  First order = generally the sensory afferent neuron (one interacting with world)  Second order = first order synapses here and this neuron crosses the midline  Third order =second order synapses her and this neuron is in relay nuclei of thalamus Dorsal Columnar (AKA medial leminiscal) Pathway: Touch, vibration, and proprioception  Ascend IPSILATERALLY in dorsal column  Synapse in gracilus and cuneate nuclei (1st order)  CROSS MIDLINE and ascend in medial lemniscus  2nd order neuron synapse in ventral posterior lateral (VPL) nucleus (On contralateral side of origin b/c crossed midline)  Third order neuron synapse in somatosensory cortex of brain Ventrolateral spinothalamic tract  Nociception and thermoreceptors synapse on dorsal horn  CROSS MIDLINE and ascend in the ventrolateral quadrant  Synapse in VPL or reticular formation  Project to thalamus  10: Physiology of Pain (Bacoat-Jones)                 Pain = Unpleasant sensory or emotional experience associated with actual or potential tissue damage Transduction = conversion of stimulus into electrical energy (nerve impulse)  Receptor molecule opens channel and depolarization occurs via influx of Na or Ca ---> AP  Anesthetics stop nociceptive signals by blocking Na channels ----> no AP (ex: Procaine) Transmission = sending an impulse across a sensory pain fiber Perception = patient’s experience of pain Modulation = inhibition of pain (through the release of inhibitory NTs) Nociceptors = a high threshold sensory receptor of somatosensory system that is capable of transducing noxious (painful) stimuli Modulation = process in which the body alters a pain signal  Explains different people’s ability to tolerate pain 5 Levels of interaction  1: Periphery = at the source of pain (cut on your finger)  2: Dorsal Horn = Gate theory of pain  Gate theory: If you rub the area around where you get injured, the nonnociceptive signals will suppress the nociceptive signals and help relieve the pain  3: Fast Neuronal Descending Pathways = facilitatory (enhance pain) or Inhibitory (suppress pain)  4: Hormonal = endogenous opiates, dopamine, NE, and serotonin  5: Cortical = Reduce pain by acting on descending pain system in brainstem Central Pain Pathways  The brain processes pain in multiple regions via different pathways  1. Location, intensity, and quality of noxious stimuli  2. Unpleasantness and autonomic activation Endogenous Opioids; Internal molecules that act like opioids to regulate pain  3 classes of peptide molecules  Enkephalins  Endorphins  Dynorphins Receptors for endogenous opioids are in the spinal cord, medulla, and periaqueductal gray matter  Can inhibit 1st order and 2nd order neurons  Can inhibit increased synaptic efficiency (hyperalgesia) Modulation begins with electrical stimulus in brain which activates the descending inhibitory nerve fibers which block the input and output of neurons  Pain Fibers  A beta: LARGE, proprioceptive fibers  A delta: small myelinated skin fibers that respond to mechanoreceptive pain  Quick, intense, acute pain  Respond to mechanical and mechanothermal stimuli  Transmit APs 10 times faster than C fibers ---> first pain  C: small unmyelinated fibers that respond to nociceptive pain  Throbbing, burning pain ---> second, longer lasting pain  Respond to thermal, mechanical and chemical stimuli Pathological Pain  Allodynia = Pain from a stimulus that is not normally painful  Dysesthesia = Unpleasant sensation  Hyperalgesia = increased pain from a stimulus that normally causes a lower level of pain  Hyperesthesia = increased sensitivity to a mild stimulus (no special senses)  Hypoesthesia = decreased sensitivity to stimulation (no special senses)  Hyperpathia = abnormally painful reaction to stimulus, especially a repetitive stimulus  Hypoalgesia = diminished response to a normally painful stimulus  Paresthesia = abnormal sensation (numbness/tingling)  Neuropathy = disturbance of function of a nerve  Neuralgia = pain in the distribution of a nerve  Analgesia = absence of pain to a normally painful stimuli Perception of Pain  Threshold = minimum intensity of a stimulus that is perceived as painful  Suggests a physiologic mechanism controlling transmission of pain signals or its interpretation  Tolerance  Drug tolerance: less efficacy in pain reduction from the same dose over time.  Require larger doses for the same effect---> increasing tolerance  Acute vs Chronic  Acute: less than 3 months, short term and curative, result of noxious stimuli  Chronic: greater than 3 months, unresolved, result of visceral or somatic nociceptors Neuropathic Pain: Pain due to damage/alteration of the somatosensory system  Usually results from a disease process affecting the system (ex: diabetes)  Shooting, electric shock like aching or burning  Does not respond well to analgesics and is usually chronic  Phantom Limb Pain: Pain in a limb that has been amputated  May be due to nerve fibers at the stump being stimulated and the brain interprets the origin of the pain as being in the amputated limb  Referred Pain: Usually from a visceral organ and is felt in a distant site from the pathology  Mechanism is potential spinal convergence of neurons for viscera and somatosensory system cutaneous, deep hyperalgesia, tenderness and muscle contractions Fibromyalgia: Chronic pain all over the body with hypersensitivity to stimuli  May be due to decreased serotonin and increased substance P  Central sensitization: perception of pain is elevated and there is an experience of pain without a noxious stimulus 11 and 12: Autonomic Nervous System I and II (Benmerzouga)           Somatic: Voluntary motor functions  Cell body in CNS and synapses with muscle via a nicotinic receptor and ACh Autonomic: autonomic reflexes like blood pressure  Afferent neurons go ASCEND from organs to brain  Efferent neurons EFF OFF from brain and go to organs  Divided into Parasympathetic and Sympathetics  Parasympathetic  preganglionic fibers that release ACH onto a nicotinic receptor on a short postganglionic fibers that release ACh onto an alpha or beta receptor on the target organ  Sympathetic  short preganglionic fibers that release ACh onto nicotinic receptors on long postganglionic fibers that release NE onto muscarinic receptors on the target organ  Fibers releasing ACh are cholinergic and fibers releasing NE (or Epi) are Adrenergic ACh ----> Parasympathetic  Made by choline acetyltransferase  Degraded by ACh esterase  Constricts pupils, constricts bronchioles, contracts detrusor muscle, erection, tears, decreased heart rate  Cholinergic Receptors are muscarinic or nicotinic NE ------> Sympathetic  Made from Tyrosine  COMT degrades  Dominates arterial tone and makes up vasomotor center  Dilates pupils, dilates bronchioles, relaxes detrusor muscle, constricts blood vessels, increases heart rate  Adrenergic receptors are alpha or beta and those are further divided into alpha 1 and 2 and beta 1 and 2 (so much more on this to come)  Alpha 2 are inhibitory and beta 2 are excitatory  Autoreceptor: respond to NT released by cell  Heteroreceptor: respond to NT released from surrounding Excitatory Postsynaptic Potentials (EPSP)  Excitatory presynaptic neurons release neurotransmitters like Ach, glutamate, NorEpi, Epi, Dopamine, Serotonin  Excitatory neurotransmitters bind postsynaptic receptors, sodium influx bringing postsynaptic neuron closer to threshold  APs only fire when neuron reaches threshold Inhibitory Postsynaptic Potentials (IPSP) Inhibitory presynaptic neurons release GABA or glycine  Inhibitory neurotransmitters bind postsynaptic receptors causing either K+ efflux of Cl- influx  Hyperpolarization, harder to reach threshold and fire AP  Ach on M2-> K+ efflux, hyperpolarization, IPSP Parasympathetic target tissue receptors  M1: Gq:PIP2->IP3+DAG, increased Ca2+,  activated PKC  M2: Gi: inhibit adenylyl cyclase  M3: Gq  Remember: odds are Gq Sympathetic target tissue receptors  Alpha1: Gq  Alpha2: Gi  Beta1: Gs: stimulate adenylyl cyclase,  increase cAMP, activate PKA  Beta2: Gs  Beta 3: Gs  Remember: all Beta is Gs