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Unit 5: Physiology TABLE OF CONTENTS 01 Content Review 02 Practice Questions 03 Q&A Chapter 6: Signal Transduction Intro to Signal Transduction Cells have to communicate with each other! - Types of communication include: - Electrical signals - Protein-protein contact - Signaling molecules - Signals...

Unit 5: Physiology TABLE OF CONTENTS 01 Content Review 02 Practice Questions 03 Q&A Chapter 6: Signal Transduction Intro to Signal Transduction Cells have to communicate with each other! - Types of communication include: - Electrical signals - Protein-protein contact - Signaling molecules - Signals cause changes in the cell that is receiving the signal For signalling molecules specifically Transmembrane protein polar - - Receptor undergoes a conformational change when bound by signal molecule → receptor then interacts with downstream proteins in the cytoplasm to cause a response Can induce both cytoplasmic and nuclear responses! Types of Cell-Cell Communication 1) 2) 3) 4) Autocrine: cell signals itself Juxtacrine: cell signals another cell in close contact (touching) Paracrine: cell signals a nearby cell not in close contact Endocrine: cell signals distant cell (often through the bloodstream by the endocrine system) “Signal” is also “Signal Molecule” which is also “Ligand” Juxtacrine Exception: Receptors in the Cytoplasm When receptors are in the cytoplasm instead of the membrane: - Ligand typically nonpolar (in order to diuse through membrane) - Ligand binds intracellular receptor which then travel to the nucleus to activate transcription In the case of the estrogen receptor, a chaperon protein is normally bound when estrogen is not - Upon binding of estrogen, the chaperon protein is released - [estrogen] + [estrogen receptor] binds the estrogen response element (ERE) Hormone estrogen Estrogen Receptor ERE binds enhancer and activates transcription G-Protein Coupled Receptors (GPCR) - Binding of a ligand to a receptor controls the activity of the downstream G-protein - Conformational change in receptor triggers conformational change in G-protein - G-protein releases GDP, binds GTP and is released from receptor (a subunit) - G-protein(GTP) binds eector protein to trigger signaling cascade - Induces both cytoplasmic and nuclear responses Inactive Active Caffeine Inhibition of the Adenosine Receptor (AR) C AR C Caeine binds A AR (GDP) No conformational change - A Adenosine binds Caeine competes with adenosine binding to AR - “Competitive inhibitor” and prevents drowsiness Adenosine = agonist (activates AR) Caeine = antagonist (inhibits AR) Either adenosine or caeine bound at a time, never both at the same time AR AR (GTP) conformational change Drowsiness Ligand-Gated Ion Channel (LGIC) - Protein Kinase Receptor (PKR) Ex. acetylcholine (ligand) binds to the acetylcholine receptor which is a LGIC that opens to allow the diusion of ions (ex. Na+) - Works like Voltage-Gated Sodium Channel (VGSC) - Insulin “Kinase” is a protein that phosphorylates a target using ATP Signal transmission from protein to protein PKR phosphorylates itself (ATP) PKR-Pi phosphorylates a cytoplasmic protein PKR PKR Pi active Signal transduction pathway activated Pi Epidermal Growth Factor (EGF) Conformational change occurs once EGF bound, G-protein targets eector protein Protein Kinase Cascade - G-protein G-protein involved “Mitogen” = growth factor EGF Receptor Active TF MAP3K = mitogen activated protein kinase kinase kinase MAP2K = mitogen activated protein kinase kinase MAPK = mitogen activated protein kinase “Domino” Eect where each kinase acts on another kinase until end target for activated transcription. cAMP acts as a 2nd messenger - - 1st messenger: signal molecule (ligand) binds to receptor to initiate cellular response 2nd messenger: cytoplasmic signal molecule involved in signal transduction pathway - Ex: cAMP, Ca2+, phosphatidylinositol triphosphate, nitric oxide 1st messenger glycogen 2nd messenger (active) PKA (inactive) —> PKA(cAMP) (active) Stimulate glycogen breakdown Glucose - 1 phosphate released into blood Turning off Signal Transduction Pathways Phosphatase removes Pi active protein protein inactive Pi GTPase G-protein G-protein active inactive GDP GTP cAMP active Pi Phosphodiesterase AMP inactive Which type of cell signaling requires physical contact between the signaling cell and receiving cell? a) b) c) d) Endocrine signaling Autocrine signaling Juxtacrine signaling Paracrine signaling Which type of cell signaling requires physical contact between the signaling cell and receiving cell? a) b) c) d) Endocrine signaling Autocrine signaling Juxtacrine signaling Paracrine signaling Which characteristic(s) is correct of caeine? a) Agonist b) Antagonist c) Competitive inhibitor of adenosine d) Activates drowsiness Which characteristic(s) is correct of caeine? a) Agonist b) Antagonist c) Competitive inhibitor of adenosine d) Activates drowsiness Chapter 31: Nervous System Pt 1 Brain Anatomy Cerebrum Pons and cerebellum Neural tube (2-4 weeks) = precursor of brain that becomes more developed over time Structures to know - Cerebrum - Glands - Midbrain - Pons - Cerebellum - Medulla - Spinal cord Spinal cord CNS vs PNS Central nervous system : CNS - Brain + spinal cord brain Eerent neurons (cause eect) Peripheral nervous system : PNS - Nerves outside the brain and spinal cord Neuron: single electrically excitable cell with long axons Aerent neurons (input) Spinal cord Nerves: bundles of axons or neurons Neuron Structure Neuron Structure: The Presynaptic Neuron passes on the electrical signal while the Postsynaptic Neuron is the recipient ↳ However, both of these terms are relative. - Dendrites: Input from other neurons - Cell Body: Contains organelles - Axon Hillock: At the cell body/axon border - Axon: Conducts the signal - Synapse: Connects axon terminus to dendrites of Postsynaptic Neuron Neuronal Support Cells Glial Cells - Are a type of cell that supports nerves and protects axons - Astrocytes: Link Axons to capillaries (blood flow) - Myelin Sheath: Surrounds the axons - Oligodendrocytes: Found in CNS axons - Schwann Cells: Found in PNS axons Brain Coordination With Sensations How does a signal like pain reach our brain to coordinate a response ? The nerves in our spinal column are in ascending (aerent) and descending (eerent) tracks of axons. - An Aerent signal, meaning moving through our spinal cord towards the brain: Dorsal Root →Ventral Horn - An eerent signal, meaning moving away from our brain back through the spinal cord: Ventral Root →Ventral Root ☆ Neurons for the left side of body mirror neurons on right side of the body - They reciprocate in reverse directions! Interneurons - Knee Jerk Reflex Interneurons are mostly found in our CNS and are kind of like “short-cuts” ↳ They are responsible for quick reactions without brain involvement Ex: Knee Jerk Reflex - Tapped on the knee sends a signal to the spinal cord - There is an axon split in the vertebrae: - 1st Synapse sends eerent signal to contract upper thigh - 2nd Synapse send eerent signal to relax lower thigh muscle - That dierential signal after the 2nd Synapse is facilitated by interneurons! Neuron Electrical Potentials If we could zoom into the axon of a neuron, we can find an ion imbalance inside and outside the membrane of the axon. This is an imbalance of potential energy called Membrane Potential composed of two parts: 1. Electrical Potential: Charge imbalance 2. Chemical Potential: Concentration imbalance Combined, this is the Electrochemical Potential ↳ This generates a voltage that can drive ions to move across the membrane Major Ions Involved in Neurons: Cl– HPO42Na+ K+ Ca2+ Current of Ions Across a Membrane Ohm’s Law: Voltage = Current x Resistance ↳ Membranes are impermeable to ions, Resistance = Infinity ↳ If the ions can’t move across the membrane, the resistance is infinite and the current is 0. The only way the current can flow across the membrane is via permeases or transporters. How Ions Move Across Membranes Active Transport One mechanism for ions to move across a membrane is Active Transport Ex: Sodium Potassium Pump (ATPase) - An antiporter simultaneously moving 2 K+ through the membrane into the axon and 3 Na+ outside of the membrane - Requires ATP hydrolysis to facilitate this transport How Ions Move Across Membranes Facilitated Diffusion In the nervous system, Ion channels are “gated” meaning they open and closed under certain conditions: - Voltage Gated Channels: Respond to voltage changes across a membrane - Chemically Gated Channels: Respond to molecules that bind/alter channel protein - Mechanically Gated Channels: Respond to force applied to membrane They all control ion flow in a regulation fashion! Neuronal Voltage Gated Channels Na+ Channel K+ Channel Na+/K+ Pump -60 mv (Resting Potential) Closed Closed On -50 mv (Threshold) Open Closed On +50 mv Closed Open On When open, Na+ rushes into neuron When open, K+ rushes out of neuron After the discharge of Na+ through the Sodium channel and K+ through the Potassium channel, both ions are at equilibrium. Sodium/Potassium pump (ATPase) reestablishes the Na+ gradient and the K+ gradient. Movement of Action Potential Down Neuron Voltage Time Plot: 1. 2. 3. Time 1 2 3 4 5 mV -60 -50 +50 -70 -60 Na+ C Open C C C K+ C C Open C C 4. 5. Time =1, mV = -60 (Resting Potential) Na+ Channel: Closed , K+ Channel: Closed Time = 2, mV = -50 (Threshold) Na+ Channel: Open, Na+ rushes into axon while K+ Channel: Closed Time = 3, mV = +50 Na+ Channel: Closed, K+ Channel: Open, K+ rushes out of axon Time = 4, mV = -70 Na+ Channel: Closed, K+ Channel: Closed Between Time 4 → Time 5: Na+/K+ Pump moves Na+ from inside to outside and K+ from outside to inside to establish gradient Time = 5, mV= -60 (Returned to Resting Potential) - Na+ Channel: Closed , K+ Channel: Closed Notes About Action Potentials: An action potential takes about 0.01 seconds to travel down typical neuron An action potential at any point in axon is all or none → entire K+ and Na+ gradient dissipates at time = 4 on our figure. + ↳ Ex: Voltage-gated Na channel stays open until the entire Na+ gradient is dissipated (Na+ equilibrium) Synapses Where the terminal end of our presynaptic neuron and our postsynaptic neuron meet is our Synapse! ↳ The synapse transmits an electrical signal from a neuron to another (potentially other kinds of cells like muscles) 1. Electrical Synapse: Neurons are joined by gap junctions and electrical signals are passed on directly via ion flow 2. Chemical Synapse: Neurotransmiers transmit a signal between neurons through a synaptic cleft Chemical Synapse - Acetylcholine Acetylcholine (ACh)is in vesicles in the Presynaptic Cell 1. The electrical signal reaches the synapse 2. Triggers vesicle to fuse with the membrane of the Presynaptic cell 3. ACh is released into synaptic cleft 4. ACh binds with receptors in our Postsynaptic cell 5. Triggers action potential - In a postsynaptic neuron, propagates action potential - In a postsynaptic muscle cell, triggers a contraction Neurotransmitters to Know! 1. Amines: - Acetylcholine 2. Amino Acids (Glutamate, Glycine) 3. Peptides (Insulin, Glucagon) 4. Other - Adenosine Neurons often respond to inputs from many synapses 1) 2) Synaptic signals can be: a) Positive (depolarization) excitatory synapse b) Negative (hyperpolarization) inhibitory synapse Neurons respond to sum of all inputs at the axon hillock - - - “Spatial summation” from multiple synapses - Each synapse provides a small voltage, which is NOT enough to elevate the resting potential (-60mV) to threshold potential (-50mV) - If multiple synapses are activated simultaneously, the sum can reach the threshold potential - Action potential is triggered “Temporal summation” - One single synapse may fire multiple times rapidly - Able to achieve the threshold potential - Action potential is triggered Summation of input signals occurs in Axon Hillock How does an AP propagate down an axon? - Moves like an ocean wave Next 1) 2) 3) 4) channel: Senses adjacent charge change Reaches threshold (-50mV) NA+ channel opens NA+ ions rush in Ions moved in and out of membrane at fixed positions outside Inside axon AP moves The net flow of K+ at A is (A, B, or C)? The net flow of K+ at B is (D, E or F)? The net flow of K+ at C is (G, H, or I)? The net flow of K+ at D is (J, K, or L)? A. Into the Neuron B. Out of the Neuron C. Neither Into or Out of the Neuron D. Into the Neuron E. Out of the Neuron F. Neither Into or Out of the Neuron G. Into the Neuron H. Out of the Neuron I. Neither Into or Out of the Neuron J. Into the Neuron K. Out of the Neuron L. Neither Into or Out of the Neuron The net flow of K+ at A is (A, B, or C)? The net flow of K+ at B is (D, E or F)? The net flow of K+ at C is (G, H, or I)? The net flow of K+ at D is (J, K, or L)? A. Into the Neuron B. Out of the Neuron C. Neither Into or Out of the Neuron D. Into the Neuron E. Out of the Neuron F. Neither Into or Out of the Neuron G. Into the Neuron H. Out of the Neuron I. Neither Into or Out of the Neuron J. Into the Neuron K. Out of the Neuron L. Neither Into or Out of the Neuron Match the answer with the question: Output Digestion A. Aerent/Conscious B. Aerent/Unconscious C. Eerent/Conscious D. Eerent/Unconscious Input Taste A. Aerent/Conscious B. Aerent/Unconscious C. Eerent/Conscious D. Eerent/Unconscious Match the answer with the question: Output Digestion A. Aerent/Conscious B. Aerent/Unconscious C. Eerent/Conscious D. Eerent/Unconscious Input Taste A. Aerent/Conscious B. Aerent/Unconscious C. Eerent/Conscious D. Eerent/Unconscious Chapter 33: Muscle Structure of Skeletal Muscle : made up of many muscle fibers or “Muscle Fiber”: 6 myofibrils inside sheath : many sarcomeres linked end-to-end Sarcomere: 1 unit of contraction apparatus Contains actin filaments and myosin filaments Sarcomere —> myofibril —> muscle fiber —> skeletal muscle Sarcomere Contraction - Z lines ends sarcomere (protein) M band marks the middle (protein) Contraction 1) More actin/myosin overlapped 2) Z lines move closer to M band What changes: - A band (No) - I band (smaller) - H zone (smaller Sliding Filament Model for Contraction a) b) c) Actin filament interacts with myosin filament Actin and myosin slide past each other, such that more actin/myosin overlap in contracted muscle Requires ATP hydrolysis and is triggered by Ca2+ increase in sarcoplasm Actin: 2 strings of pearl beads wrapping around each other - Tropomyosin wraps around actin Troponin (regulatory) to which Ca2+ bind to trigger increasing actin/myosin overlap “Power Stroke” Myosin: 2 ropes wrapping around each other Sliding filament model: actin slides by myosin using “Power Stroke” Which ordering of muscle units from the smallest to largest is correct? a) myofibril —> sarcomere —> muscle fiber —> skeletal muscle b) sarcomere —> myofibril —> muscle fiber —> skeletal muscle c) skeletal muscle —> muscle fiber —> sarcomere —> myofibril d) muscle fiber —> myofibril —> sarcomere —> skeletal muscle Which ordering of muscle units from the smallest to largest is correct? a) myofibril —> sarcomere —> muscle fiber —> skeletal muscle b) sarcomere —> myofibril —> muscle fiber —> skeletal muscle c) skeletal muscle —> muscle fiber —> sarcomere —> myofibril d) muscle fiber —> myofibril —> sarcomere —> skeletal muscle Which regions of the sarcomere changes in size during contraction? a) Z line, A band b) M band, H zone c) I band, H Zone d) A band, I band Which regions of the sarcomere changes in size during contraction? a) Z line, A band b) M band, H zone c) I band, H Zone d) A band, I band Thank You!