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Human Physiology - TEST I.doc

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Human Kinetics
HK 2810
Coral Murrant

1. The action potential is a single event occurring on one specific spot on the membrane of a neuron, but some neurons are a meter long. Describe the processes that lead to the propagation of the action potential down the length of a neuron? How does myelin wrapped around the neuron change these processes? Answer: At resting potential (-70mV), the cell is unstimulated, having a separation of charge (-ve inside, +ve outside). When AP is generated at one point on membrane, it sets another separation of charge which causes bidirectional spread of charge from that point via local current. Local current decays over distance because there are protein pores that allows transmembrane leak and because not all ions move longitudinally. As it moves down the axon, adjacent patch of membrane depolarizes, causing voltage gated Na+ channel to open and generate another AP. Action potential doesn’t go backward because there is brief period called refractory period when no AP can be generated even in presence of stimulus. The absolute refractory period is due to saturation of Na+ channel or inactivation of Na+ channel. The AP generated propagates down the axon. Speed of conduction depends on the size of neuron and whether or not it is myelinated. The larger neuron has greater conduction velocity, and myelinated neuron has greater conduction velocity. Myelin is the membrane of schwann cell wrapped around the axon fiber and it works as insulation against transmembrane leak therefore less decay of local current occur. Between schwann cells there is a region called Node of Ranvier which is packed with voltage gated Na+ channel and K+ channel(machinery to generate AP). Myelinated neuron conducts very fast conduction called “salutatory conduction” (AP jumps from one Node of Ranvier to another). The speed can be as fast as 120m/s 2. Diagram the change in membrane potential that occurs over time during an action potential in a neuron and describe the channel and ion movement that produced these changes. At what time point does the relative refractory period occur? Explain the mechanistic basis of the relative refractory period Answer: At resting potential (-70mV), the cell is unstimulated, but once membrane potential reaches -65mV~-60mV(threshold potential), fast Na+ channel opens allowing Na+ flux in. After 1-2ms, Na+ channel inactivates, and Na+ flux stops and membrane starts to repolarize. As membrane potential gets closer to 0mV, slow K+ channel slowly opens allowing K+ flux out which accelerates repolarization of membrane. Approximately 0.5-1ms after inactivation of Na+ channel, Na+ channel starts to close so that it can be reopened. After that, K+ channel slowly starts to close, but since it’s a slow process, K+ will continuously flux out until the channels are completely closed. This leads to hyperpolarization. During relative refractory period, you need greater stimulus than original to generate AP. After Na+ starts to close, Na+ channel can be reopened which means that you can generate another AP. But since K+ channel is still opened letting K+ ion out of the cell, it’s harder to depolarize. During hyperpolarization, it’s also hard to generate another AP because the membrane potential is further away from threshold level. To reach threshold level, you need to have stronger stimulus. 3. Describe the phenomena of summation in a neuron and in skeletal muscle. What is the physiological relevance of summation? Answer: In neuron, depending on which neurotransmitter is released and bound to the post synaptic cell membrane receptor, either EPSP(excitatory post synaptic potential  depolarization) or IPSP (inhibitory post synaptic potential  hyperpolarizaiton) is generated. EPSP is from opening of ligand gated Na+ or Ca2+ channel, and IPSP is from opening of Cl- or K+ channel. One IPSP or EPSP can change membrane potential by 2mV, therefore it’s not enough to generate an AP on the membrane. Summation can occur temporally or spatially. Temporal summation occurs when AP arrives fast enough so that it can summate before the previous one levels off. Spatial summation occurs when AP from many axons arrive at the same time. It works the same for EPSP and IPSP and EPSP and IPSP can cancel each other out. In skeletal muscle, as you increase the AP frequency, the summation of force occurs instead of summation of membrane potential. Each AP allows the cell to release certain amount of Ca2+ from Sarcoplasmic Reticulum and this released Ca2+ binds troponin and allows Actin-Myosin interaction to occur so that contraction can take place. As AP frequency increases, 2 AP can arrive and generate force before the force of 1 AP is gone, therefore there is going to be more force than would have been generated from a single AP. If AP frequency is fast enough, the maximum force will be reached, and it’s called “fused tetanus”. 4. Beginning at the level of the t-tubule, describe the processes involved in generating force in skeletal muscle in response to a single action potential. How would the process differ if the muscle were stretched longer than optimal length for force generation? Answer: Membrane is far from sacromere where actual contraction takes place; membrane invaginates through z-line making t- tubule. AP at membrane propagates down through t-tubule and cause conformational change on voltage sensitive protein DHP. DHP, RyR and Sarcoplasmic reticulum are all physically connected, therefore conformational change in DHP cause chain reaction through RyR and finally opens SR, releasing Ca2+ into cytoplasmic space. Cytoplasmic Ca2+ binds Ca2+ binding protein troponin, and this binding (Ca2+-Troponin-Tropomyosin) removes tropomyosin inhibition by exposing actin binding site on myosin. ATP bound Myosin hydrolyzes itself forming Myosin-Pi-ADP. This molecule has high affinity for actin so myosin head binds actin. Actin-Myosin- Pi-ADP then undergoes reaction which releases Pi and ADP from the molecule. This reaction makes the myosin head to tilt generating powerstroke, pulling actin fibers toward each other. Myosin-Actin binds ATP and this complex releases actin because it has low affinity for actin. Since there is no other AP coming in, DHP goes back to normal configuration which makes the RyR and SR back to normal, closing Ca2+ channel. ATPase on SR membrane actively pumps Ca2+ back to SR to restore intracellular Ca2+ storage and remove cytoplasmic Ca2+. The amount of force generated is closely related to the length of muscle. If the muscle were stretched longer than optimal length, there will be less or no actin myosin overlap, so less or no actin myosin interaction takes place. Since amount of A-M myosin is proportional to amount of force, stretched muscle will generate less force than the optimally lengthened muscle. 5. You step onto an elevator and there is your favorite entertainer of all time. Describe how you perceive and identify the individual. Focus your answer in the visual system beginning with the ganglion cell Answer: All 3 types of ganglion cells (P, M, & W) are circle-surround receptive field that detects points of lights and they notice information about wavelength and intensity of light of what I am seeing. P carries wavelength info at intermediate speed, M carries intensity info at fast speed, and W carries intensity info at low speed. The P & M ganglion cells synapses at Lateral Geniculate Nucleus of the thalamus. LGN also contain circle-surround receptive field that detects points of light. Info from left side of both eyes goes to left side of LGN and info from right side of both eyes goes to right side of LGN. Information is remaining segregated in the LGN. M & W ganglion cells synapses at Superior Colliculus’s superficial layers which are dedicated for vision. Other 4 deep layers are dedicated for other sensory information such as auditory or somatosensory information. Info from both the LGN and SC travels by neurons to synapse at Primary Visual Cortex. In PVC, there are simple, complex, and hypercomplex cells which perceive lines of light, movement & orientation of lines, and angles, motions & direction, respectively. All three types of cells form functional column. However, after the detection of features, information needs to go to new places to identify the person. Info travels to the temporal lobe which contains information to identify the person, and to the parietal lobe for spatial perception of the person. 6. Ganglion nerve cells are unmyelinated as they cross the retina and myelinated as they leave the eye through the optic disc. Assuming that an action potential is started in a ganglion cell, describe how an action potential is propagated down the unmyelinated part of the neuron. Describe why the speed of propagation in the myelinated region changes? Answer: Ganglion cell is not myelinated because it may block photon coming in which will compromise visual acuity. Unmyelinated nerve cells have slower conduction velocity because there are transmembrane leaks that facilitate decay of local current. AP from one point cause longitudinal separation of charge which cause bidirectional spread of +ve charge (inside). When adjacent area’s membrane potential reaches threshold, another AP generated. It was shown that 37% of initial charge is observed over 1-2mm, therefore every 1-2mm there are voltage gated Na+ and K+ channel to generate another AP. As AP propagates down the axon, it doesn’t move backward because of refractory period. Refractory period is occurs when voltage gated Na+ channels are either open or in the inactive state thus no more channels can be opened. The conduction speed of unmyelinated cell is approximately 5m/s. Once the cell is myelinated, the speed of propagation increases upto 120m/s. Myelin is the schwann cell wrapped around the axon fiber which provides insulation against transmembrane leak (preserve local current). Between schwann cell, there is a region called Node of Ranvier which is packed with AP generating machinery. So instead of moving down the axon, AP jumps from one node of Ranvier to another (Saltatory conduction). 7. Experimentally skeletal muscle fibers can be activated to contract using a single action potential. Describe the processes of muscle contraction and force generation resulting from a single action potential (starting at the level of the skeletal muscle t-tubule). Describe how these processes would differ if the action potential frequency was increased. Answer: AP propagates down to t-tubule which is invaginated membrane through z-line. AP causes conformational change in voltage sensitive protein DHP and physically connected RyR (bridge of receptors) and ultimately opens sarcoplasmic reticulum, the intracellular Ca2+ storage. Ca2+ from SR released and increases cytoplasmic Ca2+ concentration. This Ca2+ then binds troponin and form Ca2+ troponin-tropomyosin complex and removes inhibition on actin binding site on myosin. Now actin binds Myosin-Pi-ADP (high affinity for actin) forming Actin-Myosin-Pi-ADP complex. Then Pi, and ADP get removed from the complex causing myosin head tilt which is called powerstroke. Amount of force generated is directly proportional to amount of A-M interaction for this reason. Then ATP gets added to Actin-Myosin and Actin is released from Myosin-ATP has low affinity for actin. After the contraction, if there isn’t any other AP coming in, DHP and RyR go back to their normal conformation and SR closes its Ca2+ channel. Cytoplasmic Ca2+ get actively pumped back to SR via ATPase on SR, and tropomyosin inhibition block the A-M interaction, therefore no contraction occurs. But if there are more AP coming in (high AP frequency), more Ca2+ will be released, removing more inhibition on myosin head actin binding site, which in turn allowing more A-M interaction which is proportional to amount of force generated. So if AP frequency is increased, instead of removing cytoplasmic Ca2+, the more Ca2+ release will occur, generating more contraction (force) in muscle fiber. 8. For any external stimuli to be sensed by the body that external stimuli must be converted into a change in membrane potential and eventually produce an action potential. Describe in detail, the process of how a photon could change the action potential frequency of a ganglion cell Answer: Photon travels into the eye and gets absorbed by pigment epithelium, the dark layer, so that it won’t bounce around. There are two types of photoreceptors, rods and cones. Rods are very sensitive and detect intensity of light (brightness) and cones are less sensitive and detect wavelength/color of what is coming in. When photon comes in, photon gets absorbed by rhodopsin and rhodopsin undergoes conformational change which turns transducin(G protein) on. G protein activates cyclic GuanineMonoPhosphate phosphodiesterase which catalyzes the reaction from cGMP to 5’GMP. As the reaction proceeds, concentration of cGMP decreases within cell, which will decrease the number of cGMP dependent Na+ channel opened. Closed Na+ channel results in hyperpolarization and decreased Glu release from a rod cell. If the post synaptic cell is Off bipolar cell(AMDA Rm), it hyperpolarizes in response to decreased Glu. If the post synaptic cell is On bipolar cell, it depolarizes in response to decreased Glu. In case of RBG pathway, bipolar cell directly synapses with ganglion cell. RBG pathway has the least amount of synapses therefore there is least amount of integration occurred to the visual information. If not RBG pathway, it travels down the horizontal cell, and interplexiform cell via change in membrane potential, and as it reaches amacrine cell, it may generate AP to propagate down to ganglion cell, or it may travel via change in membrane potential as previous conduction. When it reaches ganglion cell, depending on summated membrane potential (either hyperpolarization or depolarization), ganglion cell generates AP or don’t generate AP. If there were many depolarization events, ganglion cell reaches threshold easier and AP frequency is faster. 9. Compare and contrast end plate potential, EPSP, IPSP, generator potential and action potential. In your answer, consider functional and mechanical aspects of each potential Answer: All describe change in membrane potential, by changing the membrane permeability (opening and closing of channels) to ions. Also EPSP, IPSP, generator potential and endplate potential are sub-threshold changes that can summate either spatially or temporally to bring a large change in membrane potential. EPP, EPSP and AP are changes in membrane potential that bring the post synaptic cell closer to threshold while IPSP brings the post synaptic cell further from threshold. Generator potential can go either way depending on the nature of the receptor or stimulus. End plate potential: in neuromuscular junction, as Nicotinic Cholinergic Na+ channel opens causing depolarization. The change in membrane potential summates and ultimately generates another AP in post synaptic membrane, ligand gated channel EPSP: Excitatory Post Synaptic Potential; opening of Na+ or Ca2+ channel which brings in positive ion to the cell causing depolarization, Occur between neurons, ligand gated channel IPSP: Inhibitory Post Synaptic Potential; opening of K+ or Cl- channel which brings in Cl- ion or move K+ out of the cell causing hyperpolarization. Occur between neurons, ligand gated channel. Generator potential: change in membrane potential from free nerve ending or specialized nerve ending. Using ligand gated channel, enzyme dependent channel or direct deformation Action potential: sudden change in membrane potential at specific point in response to a stimulus. Occur at nerve or muscle cells, voltage gated channel 10. Diagram the monosynaptic reflex and indicate the role that local current plays in function of the reflex arc Answer: In sensory neuron(stretch receptor), local current promotes the generation of the initial AP by transmitting changes in membrane potential to areas that can produce an AP. Local current ensures the propagation of AP down the sensory neuron axon(afferent). Local current opens voltage gated Ca2+ channel to promote neurotransmitter Glu release (Glu- for EPSP, Gly- IPSP). Local current extends the EPSP from dendrite+soma (no machinery to generate AP) to the axon hillock(packed with voltage gated Na+ and K+ channel) of the post synaptic neuron(motor neuron) to generate an AP. Local current ensures the propagation of AP down the motor neuron(efferent) opening voltage gated Ca2+ channel to promote Ach release. Local current extends the end plate potential to regions that can produce AP. Local current ensures the propagation of the AP along the skeletal muscle fibers. Local current alters voltage gated channels which leads to the opening of Ca2+ release channels from the SR 11. Describe the ion channel and charge movement thought to produce the absolute and relative refractory periods, and discuss the implications of the refractory periods on generation and propagation of an action potential Answer: Absolute refractory period is the period during an AP where another AP cannot be produced even in a presence of stimulus. It occurs over when all voltage gated Na+ channels are either open or in the inactive state thus no more channels can be opened. Inactive Na+ channels cannot be reopened until it becomes closed. Relative refractory period is the period where AP is generated only in presence of greater stimulus. Initially depolarization is harder to achieve because K+ channel is still opened fluxing K+ ion out of the cell while Na+ channel are in closed state, can be reopened. Thus any stimulus that tends to open Na+ channels will have difficult time depolarizing as K+ is moving out to hyperpolarize at the same time. Open K+ channels eventually hyperpolarize the membrane potential below resting membrane potential and a stronger than normal stimuli is required to reach threshold because we are further away from threshold. Implication of absolute and relative refractory period give directionality to AP (AP cannot go backward) and as there is a region where another AP cannot be generated, it also set max firing rate of AP 12. Outline the signal transduction involved in a rod photoreceptor when going from a dimly lit room to complete darkness Answer: In a dimly lit room, photon hits rhodopsin and rhodopsin undergoes conformational change which stimulates transducin (G protein). Transducion activates cGMP phosphodiesterase catalyzing reaction from cGMP to 5’GMP. As cGMP concentration decreases in the cell the number of cGMP dependent Na+ channel opened decreases causing hyperpolarization of the membrane. At the end of axon terminal, amount of Glutamate released decreased because of hyperpolarization. Going into complete darkness would result in a decrease in the rhodopsin activation and a decrease in transducin activation which would decrease the activity of cGMP phosphodiesterase therefore decreasing cGMP degradation resulting in increased cGMP levels. This would increase the number of cGMP dependent Na+ channel open and increase Na+flux into the cell and depolarize the cell thereby increasing Glu release. 13. Describe the phenomena of summation in a skeletal muscle at optimal length. What would differ in a muscle that is stretched beyond optimal and why? What is the physiological relevance of summation? Answer: A single AP in muscle will result in a certain amount of Ca2+ release from SR which results in a specific amount of force generated which is called twitch force. If another AP is delivered before the effects of the first AP on force are gone, the force of the second AP will add to the first and the result is more force than would have been generated from a single AP. In a muscle stretched, the process of summation would be the same but we would get less force out of the muscle at same AP frequency. As the muscle stretches, less actin and myosin can overlap which will decrease the amount of A-M interaction which will turn decrease amount of force generated each time. Summation allows a greater response to be produced than a response from a single AP. AP has its set size but we can generate a whole range of forces from twitch to maximal tetanic contractile force depending on the AP frequency that we deliver it at. 14. Activation of the cross extensor reflex involves eventual activation of hip reflexors and inhibition of hip extensors on the ipsilateral side. Describe the events involved in the transmission of the action potential from the alpha motor neuron to the hip flexors. How would this process differ from the events at the hip extensors Answer: At hip flexors, AP propagates down the alpha motor neuron via local current, and opens voltage gated Ca2+ channel causing fusion of Ach vesicle to plasma membrane. Ach diffuses across the synaptic cleft, binds nicontinic cholinergic membrane receptor(or degraded by enzyme, or taken up by presynaptic cell) and opens Na+ channel causing depolarization at the end plate region of post synaptic cell which is hp flexor cell. Local current transmits changes in membrane potential to region with voltage gated Na+ and K+ channel, gets to threshold and begins a new AP in skeletal muscle membrane. At hip extensors, no AP comes down to the motor nerve so nothing happened (inhibited) 15. You are at the Keg after your physiology test, and the bartender has just put very large beer down in front of you. Describe how you perceive the glass of beer and identify it. Focus your answer in the visual system beginning with the bipolar cell Answer: Bipolar cell have circle surround receptive fields and perceive the beer as points of lights. Depending on the wiring, bipolar cells directly synapse with ganglion cell (RBG pathway) or synapse with horizontal, interplexiform, or amacrince cells. Amacrine cells have circular receptive field either all off, on or mixed, and at the level of amacrine cell, points of light are perceived. Ganglion cells also have circle surround receptive fields which perceive points of light. At this level, light information is processed in different types of ganglion cells. P cell processes wavelength information of light in intermediate conduction speed. M cell processes intensity of light in very fast conduction speed. Lastly W cell processes intensity of light in low speed. P and M cell goes to Lateral Geniculate Nucleus while M and W cell goes to superficial layers of Superior Colliculus. LGN has circle surround receptive fields and still perceive points of light. Visual information is gathered in primary visual area where new information is integrated from dots of light. Simple cells, complex cells, and hypercomplex cells perceive lines, multiple inputs from simple cells, and movement, angle, & direction, respectively. Even after this, whole picture is not constructed here, so this information must go elsewhere to identify the beer. Temporal lobe contains information on absolute size and orientation of object which helps identification of object (memory), and parietal lobe contains information on spatial recognition. 16. Norepinephrine increases phosphoplipase C activity in vascular smooth muscle which results in an increase in intracellular calcium. Describe the process of force generation following this increase in intracellular calcium. How would a decrease in length of the muscle affect this process? Answer: Cytoplasmic Ca2+ binds calmodulin(Ca2+ binding protein) and this complex activates MLCK(myosin light chain kinase) which phosphorylates myosin (Myosin + ATP  Myosin-Pi+ ADP) and Myosin-Pi binds another ATP and cleaves it to ADP and Pi (Myosin-Pi-Pi- ADP) This complex has high affinity to actin so it forms Actin-myosin-Pi-Pi-ADP. ADP and Pi get released from the complex, causing myosin head tilt (conformational change  powerstroke) which is a force generating step. Now Actin-Myosin-Pi binds another ATP and this has lower affinity for actin, so actin gets released from the complex. Phosphorylated myosin cleaves the ATP to ADP and Pi and binds actin and the cycle continues. The process itself would not be affected by the decrease in length of muscle. But overall force generated would decrease because actin-myosin overlap isn’t optimal. 17. Ejection of blood from the heart relies on shortening of cardiac muscle fibers initiated by spontaneous generation of action potential. Describe the process involved in cardiac muscle fiber shortening and subsequent relaxation in response to a single action potential beginning with how the action potential on the t-tubule membrane changes intracellular calcium. Would you expect that there is a length tension relationship in the heart? Explain your answer Answer: AP propagates down the t-tubule, sets up a local current, changes the electrical field around the voltage gated Ca2+ channel and opens L-type voltage gated Ca2+ channel allowing extracellular Ca2+ to move into the cell. This Ca2+ works as a trigger Ca2+
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