Exam I: Nerve-Muscle Flashcards
The Nernst Equation & Interpretation
The equilibrium potential of an ion is found by this equation. The equilibrium potential is the voltage at which there is no net movement of a particular ion across the membrane, because the force of the concentration gradient is exactly balanced by the force of the electrical gradient.
The GHK Equation & Interpretation
This equation calculated the predicted resting membrane potential of the cell given the relative permeability and concentrations of the ions.
If both Na+ and K+ channels are activated by depolarization, why do we see more Na+ flux during the rising phase of an action potential?
Although both channels are activated by depolarization, the Na+ channels open quickly allowing rapid Na+ entry into the cell. The peak of Na+ permeability coincides with the peak of the action potential, while the K+ channels open more slowly and don’t reach their peak ion permeability until the falling phase of the action potential.
Discuss the membrane permeabilities of major ions and how they contribute to the overall resting membrane potential of neurons.
The average resting membrane potential is -70 mV. It is primarily determined by the concentration gradient of K+ and the membrane permeabilities of K+, Na+, and Cl-.
The equilibrium potential for K+ predicted by the Nernst equation is -90 mV. The resting membrane potential is morepermeable to K than Na. However, because the cell’s resting potential is more positive than -90mV theremust be another contributing ion, and it is the Na+ leak channels that allow positive Na+ ions into the cell which cause the resting potential to be slightly more positive.
If potassium channels in a neuron were blocked, would it be possible to produce an action potential? If so, describe the probable appearance of these components of a graph: threshold, rising phase, peak, falling phase, undershoot. If not, explain.
- Assuming sodium channels are functioning normally, there would still be an action potential.
- Threshold would be unaffected, because it is a property of sodium channels.
- A peak voltage will be reached when the sodium channels become inactivated; this voltage may be higher than normal since usually there is a partial canceling of the rising voltage as potassium exits.
- Without a potassium current, the falling phase would be much slower, being dependent on the sodium-potassium pump removing the sodium ions that came in.
- The undershoot would be absent because it is a result of potassium current.
In a laboratory situation, a nerve can be stimulated by applying voltage from a stimulator. If a stimulus was applied in the middle of a nerve roughly halfway between the cell bodies and the axon terminals, would resulting action potentials travel only from the stimulus point to the axon terminal? Why or why not? How is this similar to or different from the basic characteristics of an action potential discussed in this chapter? What does this tell you about the nature of the axon?
Action potentials would travel in both directions from the stimulus point, simultaneously toward the cell bodies and toward the axon terminals. This is because the axon segments on each side oft he stimulus point are presumably not refractory when the stimulus is delivered, thus there is nothing to prevent the action potentials from traveling in both directions. In normal transmission, the action potential begins where the axon starts, and travels only away from that point, not toward, because the membrane becomes refractory for a period of time after the action potential occurs. Thus, the axon is quite capable of transmitting action potentials in either direction, even though normally it is prevented from doing so.
Dr. Zoydburger has discovered a toxin produced in the venom of a poisonous marine invertebrate. Tests on lab mammals indicate that this toxin prevents sodium channel inactivation. How would this affect the action potentials produced in the neurons of a poisoned mammal?
Without sodium channel inactivation, the action potential would not repolarize as quickly, thus any function dependent upon the action potential would be prolonged, including neurotransmitter release and postsynaptic response. Also, the refractory period would not exist, thus action potentials would travel back up the axon, and down again, repeatedly.
Explain the processes that lead to the exocytosis of neurotransmitter from a presynaptic cell. Which components are recycled? Which ion is important in triggering exocytosis?
Action potential arrives in synaptic terminal, and stimulates opening of voltage-regulated calcium channels. The resulting calcium influx triggers exocytosis of synaptic vesicle contents. The phospholipids of the vesicle membranes are recycled, either from fusion of vesicles then later formation of new vesicles from the same molecules; or from the kiss-and-run model, in which the vesicle phospholipids are not incorporated into the membrane at all, but remain as vesicles that can be refilled
What factors determine the maximum frequency of action potentials conducted by an axon?
Maximum frequency is mostly dependent upon the duration of the absolute refractory period, which determines the upper limit. The diameter of the axon, amount of myelination present, and the magnitude of the Na+ and K+ gradients across the axonal membrane all affect action potential velocity may also play a secondary role.
Draw a graph showing change in membrane permeability (don’t worry about including the units of permeability) to sodium and potassium during the course of an action potential. For reference, superimpose a graph of the action potential.
During depolarization, PNa increase
At peak, PNa decreases
During repolarizatoin, PK increases
Draw a graph showing what would happen to resting membrane potential over time, if the sodium/potassium pump were not functioning. How would this affect a neuron’s ability to produce action potentials? What does this imply about the quantity of ions that normally cross the membrane during the course of an action potential?
It would be appropriate for the student to draw action potentials on the graph beginning at the point where the resting potential drifts up to threshold, and decreasing in frequency as the resting potential approaches. Very gradually, a cell’s resting membrane potential would increase until it reached and stabilized there. At that point the ions would be in equilibrium, and no further net flow of charge would occur. There would be no effect on ability to generate action potentials initially, but with the disappearance of the differential distribution of sodium and potassium upon which the action potential depends, action potentials would gradually come to a stop. This points out the fact that during any single action potential, so few ions cross the membrane that there is no significant change in ion concentrations. Thousands of action potentials would be required before the absence of the sodium-potassium pumps would be noticeable.
Draw graphs showing the effect on action potentials in a cell following effective doses of each of the listed neurotoxins. Assume that the cell is normally brought to threshold by an electrical stimulus applied to it, so that any abnormality is due to the toxin. Precise values for voltage and duration are not important, just a general trend in how the action potential may be different from normal.
1. puffer fish poison (blocks voltage-gated sodium channel activation) 2. tetraethylammonium (blocks voltage-gated potassium channels) 3. ouabain (blocks sodium-potassium pumps) 4. sea anemone toxin (blocks voltage-gated sodium channel inactivation)
- no action potential; membrane potential would show a stimulus pulse that reaches threshold, however
- prolonged action potential, as repolarization is slowed in absence of potassium efflux; peak may be higher as well
- normal action potential
- prolonged action potential, as sodium influx lasts longer; peak may be higher as well
List and explain the functions of the regulatory molecules in a sarcomere, specifying how the on and off positions are controlled and its impact on the crossbridges formed.
Troponin and tropomyosin and the primary regulatory proteins. Tropomyosin wraps around the actin of the thin filament to restrict access of the myosin to its binding site on the actin molecule. When intracellular calcium concentration is low such that troponin is not bound by calcium (restingmuscle), the tropomyosin is in the off position and myosin is weakly bound to actin (low force crossbridge). When muscle is stimulated, the increasing calcium binds to the troponin (C subunit) to shift the tropomyosin into the on position. In the on position, the crossbridges that are formed are high force.
Explain the events leading up to a skeletal muscle twitch, starting with the arrival of neurotransmitter in the neuromuscular junction.
Acetylcholine binds to its receptor (nicotinic cholinergic) on the skeletal muscle cell membrane. This increases in flux of cations across the membrane of which the influx of Na is greater than the efflux of K, which causes the membrane to depolarize (end-plate potential). This depolarization activates the voltage gated Na channels responsible for an action potential and the action potential travels along the sarcolemma. In addition to the sarcolemma, the action potential travels along the T-tubule causing change in the L-type Ca channel (dihydropyridine receptor) that is linked to a ryanodine receptor in the sarcoplasmic reticulum. This opens the ryanodine receptor causing calcium to diffuse out of the sarcoplasmic reticulum. The calcium binds to troponin and moves the tropomyosin out of the way such that a high force crossbridge can form between actin and myosin. The myosin head is then able to undergo its power stroke and force is generated.
Describe the process of relaxation of a skeletal muscle fiber.
Relaxation is an active process, resulting from loss of acetylcholine from the receptors as ACh is broken down and there is no further release. This allows the muscle cell to repolarize, which stops the release of calcium from the sarcoplasmic reticulum (SR). The pumping of calcium back into the SR causes the troponin to move the tropomyosin into a position that it allows only a low force crossbridge to form and the cell to relax.
List, compare, and contrast the types of skeletal muscle fibers based on their speed of contraction and resistance to fatigue. Give examples of where each type might be found, and why it is advantageous for each type to occur there.
- Red muscle = high endurance, but slow.
- Aerobic respiration predominant.
- Many mitochondria because red muscles undergo aerobic respiration.
- Equipped to receive abundant oxygen supply: many capillaries, many myoglobin.
- High endurance, doesn’t tire easily.
- White muscle = fast, but fatigue easily.
- Anaerobic respiration (glycolysis) predominant.
- Few mitochondria because white muscles undergo mainly glycolysis.
- Equipped for short bursts of glycolysis: stores high amounts of glycogen.
- Pink muscle = intermediate between red and white muscle.
Describe the muscle condition called tetanus. Is this a normal or a pathological event? If it is normal, what is the function? If it is pathological, what is the cause? The bacterium Clostridium tetani causes a disease called tetanus or lockjaw; you may have been vaccinated against tetanus, especially if you ever had hospital treatment for a skin wound. Speculate on whether or not the name of this disease is related to the muscle condition and why the disease can be fatal.
Tetanus is a state of maintained contraction that occurs as a result of increased frequency of stimulation by the nerve that does not allow enough time between twitches for the muscle to relax. Tetanus is a normal event, which allows a muscle to develop its maximal force. The bacterial disease results in maintained contraction that is similar in charter to the tetanus that can result from high frequency muscle stimulation. The disease is fatal if respiratory muscles are unable to relax because then breathing would stop.
Explain alpha-gamma coactivation.
Alpha motor neurons control the contraction of skeletal muscle fibers. Gamma motor neurons adjust the stretch sensitivity of the muscle spindle, so that the spindle is active even when the muscle shortens. Coactivation of both sets of fibers causes the tension on the muscle spindles to be maintained as the muscle shortens; thus sensitivity to stretch is maintained.
Draw a monosynaptic reflex and a polysynaptic reflex. Label each part of the reflex pathway. Briefly explain how the two reflexes differ.
Monosynaptic reflex has a single synapse between the afferent and efferent neurons; polysynaptic reflexes have two or more synapses.
Diagram and label the knee jerk reflex. What is the physiological function of this reflex? Explain how this reflex may be important during walking, if you didn’t notice a dip in the sidewalk and stepped into it. What is the role of reciprocal inhibition? How would the reflex be affected if reciprocal inhibition failed? Describe the effects on the reflex of severing each structure involved in the reflex, considering one structure at a time. Describe the effects of damaging the opposite side of the spinal cord, or areas higher or lower on the spinal cord.
- The function of the reflex is to control movement at the knee joint. If you stepped down farther than you expected, your opposite knee may bend more than it would have, activating the reflex and straightening that leg to prevent you from falling.
- Reciprocal inhibition allows muscles opposing extension of the leg to be inhibited. If this inhibition failed, leg extension would not occur; instead, the knee would be “locked.”
- Severing the afferent or efferent nerve, the spinal cord at the level of the reflex, or the muscle would all prevent there flex from occurring.
- Damage to the opposite side of the spinal cord or areas above or below the cells involved in the reflex should have no effect on the basic reflex.
Draw schematic of the cross-bridge cycle, illustrating interactions between actin and myosin and highlighting the energy states of myosin.
- Binding of actin to myosin à inorganic phosphate released
- Power stroke à actin gets pulled toward middle of sarcomere à ADP is released
- Rigor state à myosin is in low-energy form à New ATP binds to myosin head
- Unbinding of actin and myosin à ATP is hydrolyzed
- Cocking of the myosin head à myosin is in high energy form à ADP + Pi is attached
Below, action potentials have been evoked by injecting depolarizing currents into a neuron. Illustrated in A is the neuron’s response under control conditions. In B, the neuron’s response in the presence of 4-AP, a K+ channel blocker, is shown. Explain the response in A as well as the 4-AP effect.
- There’s constant depolarization in both cases.
- In (A), there is too many voltage-gated K current activated after the first action potential to permit additional action potentials to be generated. The injected current therefore cannot bring the cell to threshold thought it is sufficient to keep the cell depolarized and the K channels opened.
- In (B) some of the K channels are blocked, and the injected current is sufficient to bring the cell to threshold again after the absolute refractory period has ended.
Below the response of a neuron to two stimuli is shown. At left is a train of action potentials evoked by a long depolarizing step. Note that the action potential height is diminished by time and that the frequency of action potentials is higher at the beginning (80 Hz) than at the end of the step (50 Hz). At right are action potentials evoked by individual depolarizing steps delivered at 100 Hz. Explain why the action potential height and the neuron’s firing frequency change during a single long depolarization but not during a series of short ones.
- On the left: continuous depolarization prevents the membrane from hyperpolarizing sufficiently to allow all of the Na+ channels to recover from inactivation. Therefore the action potential frequency decreases and the action potential amplitude declines with time.
- On the right: hyperpolarization between pulses permits complete recovery of Na+ channels from inactivation.
Below are action potentials recorded with different external [Na+]. Explain, as quantitively as possible, the differences and similarities between the three waveforms.
Reducing [Na+]o has two effects: the action potential amplitude is reduced and the rising phase of the action potential is slowed. Reducing [Na+]o changes ENa. This obviously reduces the peak amplitude of the action potential.
Reducing ENa reduces INa: INa = g(Vm – ENa). I = charge/time so the rate of Na+ influx is slowed. As dV/dt = I/C, reducing I slows dV/dt
Hyperkalemic periodic paralysis is a disease that results from point mutations in the voltage-‐gated Na channel subtype found in skeletal muscle. Many of the mutations are found in the S4-‐S5 linker region, and they reduce Na channel inactivation. Affected patients experience bouts of spasm and weakness following exercise, and during these episodes, plasma K+ concentration rises, resulting in hyperkalemia. Explain how this mutation causes weakness only during exercise and why the weakness is accompanied by hyperkalemia.
Reduced channel inactivation means that there’s a tonic depolarizing Na current. This keeps the cell depolarized and prevents Na channels from recovering from inactivation and closing. Consequently, the myocytes cannot generate additional APs, and the rate of AP generation slows and force generation is reduced. Additionally, tonic depolarization keeps K channels opened, allowing K efflux. Accumulation of extracellular K exacerbates the problem by keeping the sarcolemma depolarized.
Bupivacaine, also known as Marcaine, is a Na channel blocker. It is used as a local anesthetic to relieve post-‐surgical pain. The drug is often injected near the spinal cord at the level innervating the area operated on. Describe—with as much detail on mechanism as possible—how this drug blocks pain.
It inhibits Na channels, slowing the rate of AP generation. DRG neuron firing is slowed, and propagation of signals by nociceptive afferents is reduced.
Pre-Synaptic Neuron: Explain how each designated part is significant to neurotransmitter release
- Cell body. There is an electrochemical gradient set up and a resting membrane potential by the Na/K pump and the fact that there are K+ leak channels. At rest, only the leak channels are open. Once depolarization occurs, then voltage-gated channels open.
- Ion channels. When the cell becomes more positive, S4 moves to cause conformational change in S5 and S6, the pore, to allow ions to move through it. The more positive, the more sodium channels open. Once the max positive magitude has been reached, inactivation by the N-terminus occurs.
- Initial segment with sodium channels has high resistance so more voltage is propagated (V=IR). Action potentials move only in one direction because inactivation of previous channels.
- Myelin insulated to maintain amplitude and reduce capacitance. Without myelin, the action potential will be slowed down because more charge is needed.
- Calcium voltage-gated channel. The equilibrium potential for calcium is very positive, and so calcium influx triggers neurotransmitter release.
Isotonic vs Isometric Contractions
In an isotonic contraction, the muscle contracts, shortens, and creates enough force to move the load. In an isometric contraction, the muscle contracts but does not shorten. The force created cannot move the load. Isotonic contractions have a broader and and less tension requiring plataeu for muscle relaxation.
