The action potential week 3 Flashcards
True or false: The characteristics of action potentials are exactly the same from tissue to tissue.
False. They vary. An AP in cardiac muscle looks different than in skeletal muscle. see slide 4 of notes
Action potentials are initiated by membrane ______ which causes the opening of certain voltage dependent ionic channels. Discus what types of channels open in nerve, skeletal, cardiac muscle, SA node, AV node, and smooth muscle cells.
- depolarization
- in nerves, skeletal muscle,and cardiac muscle membrane depolarization causes the opening of voltage gated Na+ channels (produces “upstroke” of AP). For SA node, AV node, and smooth muscle voltage gated Ca+ channels produce membrane depolarization
What voltage gated channels cause repolarization of the membrane in nerve and skeletal muscle?
Caused by inactivation of Na+ channels and opening of voltage-gated K+ channels. Note that Na+ channel inactivation involves a different gate and that once this inactivation gate is closed, it does not reopen until the membrane potential returns to or close to resting level. K+ channels are also activated by depolarization but they open more gradually (noticed at peak of AP)
What are some generic characteristics of APs?
- all-or-none
- non-decremental (amplitude and duration of AP do not change as it is transmitted)
- propagation
- unidirectional
- refractory periods (absolute and relative) refractory periods are major reason for unidirectional propagation. a region that has just undergone an AP cannot produce another AP
- threshold: threshold potenial is potenial at which an AP will be initated. is not a standard unvarying value
How do voltage-gated Na+ channels work? Discuss their gate(s) and the probability of their openness.
voltage-gated Na+ channels have an activation gate and an inactivation gate. At resting Vm, the activation gate is closed and the inactivation gate is open. During an AP when the membrane is depolarized, both gates are transiently open to allow for Na+ flux. The activation gate opens rapidly and after a few msec, the inactivation gate closes (closes more slowly). The closure of the inactivation gate is visualized as the peak of the AP when Na+ ions can no longer flow into the cell. (note: resting is -90 mV in cardiac and skeletal muscle and is -70 mV i.e. more depolarized in neurons)
The probability of a gate moving as well as the time required for it to move are functions of membrane potential. The probability that the activation gate will open is a function of membrane potential only. The probability of an inactivation gate being open is dependent on the fraction of Na+ channels that are available to open as a function of membrane potential.
At any point in time, a channel is either completely open or completely closed. When looking at many channels in a tissue, the probability that a channel will be activated or inactivated is more important.
There are 2 ways to close a Na+ channel: closure of the inactivation gate which occurs when the membrane is depolarized and closure of the activation gate which occurs when the membrane is repolarized.
when activation gate is close: deactivation
activation gate open: activation
inactivation gate close: inactivation
Opening of voltage gated Na+ channels drives Vm toward ENa+ (which is +60 mV) but does not quite get there (~+50mV)
How do voltage-gated K+ channels work? Discuss their gate(s) and the probability of their openness.
Note: Only discussing K+ channels in nerve and skeletal muscle
voltage-gated K+ channels only have an activation gate. This activation gate opens when the membrane is depolarized, but, on average, it opens more slowly than does the activation gate of the Na+ channel AND more depolarization is needed to open the gate. This can be seen at peak of AP when K+ flux is the most appreciable at time when voltage-gated Na+ channels have been inactivated. voltage-gated K+ channels also close more slowly than Na+ channels (K+ channels take 5 msec to close after returning to resting Vm while Na+ channels take less than one msec. reason for hyperpolarization seen in an AP: membrane potential more negative than resting). The voltage gated K+ channel does not have an inactivation gate bc once opened under physiological conditions by depolarization, it has the tendency to turn itself off due to the movement of Vm toward EK (which is about -95 mV)
Probablity of openness increases with membrane depolarization
To elicit an AP, the membrane must first be ___ by a sufficent amount.
depolarized
Discuss the positive feedback cycle of membrane depolarization as it pertains to Na+ channels and what causes this loop to cease.
As the membrane becomes depolarized, voltage gated Na+ channels open allowing inward flow (negative current by convention) of Na+. This causes further membrane depolarization as each Na+ ion drives Vm closer to ENa (+60 mV). Further membrane depolarization allow for even more Na+ current which causes this feedback loop. The positive feedback (self-sustaining process) leads to upstroke of AP but ceases when Na+ channel inactivate (due to closing of inactivation gate, a time dependent process). As voltage-gated K+ channels activate and allow for K+ efflux (positive current by convention) it drives membrane potential closer to EK
Discuss the depolarizing after potential in skeletal muscle and the reason this is observed.
During this period immediately following the action potential proper, the membrane potential is somewhat less negative than the resting potential. This is primarly caused by the T-tubule system which has a slower and more prolonged AP; in addition, due to its very small diameter but large overall surface area, there can be transient K+ accumulation in the T tubule system lumen
(hyperpolarization period seen in nerves)
Discuss the effect of hyperkalemia on membrane potential and why this is dangerous.
Hyperkalemia causes Vm to be less negative (more positive) than resting Vm. If Vm is too high, voltage-gated Na+ channels cannot be stimulated and an AP can’t be generated.
Discuss the concepts of absolute and relative refractory periods and the reasons they exist.
During the absolute refractory period, it is impossible to stimulate another AP because essentially all voltage-gated Na+ channels are inactivated and will stay inactivated until Vm returns approximately to resting level. During hyperpolarization (caused by elevation of K+ permeability due to slow closing of voltage-gated K+ channels), there is a relative refractory period during which it is relatively more difficult to stimulate an AP
Threshold is the membrane potential at which enough voltage-gated Na+ channels have been opened that the process of membrane depoalriation becomes self-sustaining. Discuss how threshold can be changed.
- Permeability of K+ and Cl- at rest affect threshold. The higher the permeability to these ions, the more depolarized the threshold potential. In inhibitory synapses in neurons, the permabilities of these ions change.
- The number of voltage-gated Na+ channels available. The more Na+ channels available, the smaller the depolarization needed to reach threshold. Similarly, if less Na+ channles are available (as can occur as the result of some toxins and a variey of drugs such as local anesthetics) then threshold will be at more depolarized potential (making it harder to fire an AP)
Discuss the concept of resting inactivation and how it affects threshold.
The rate at which the membrane depolarizes can also influence threshold. In order to be effective in initating an AP the membrane must be depolarized rapidly (over a period of a few msec to a few tens of msec). If the membrane depolarizes gradually it may never produc e an AP at all. This is due to inactivation of Na+ channels which is referred to as resting inactivation. If a membrane is depolarized incrementally, say by 1 mV/second, the Na+ channels that initially were activated will be deactivated by the time the membrane slightly depolarizes in the next second. This results in a gradual decrease in the number of Na+ channels available to be activated. Is of clinical importance in diseases such as hyperkalemia or ischemic heart disease. In gradual development of hyperkalemia, can get gradual membrane depolarization that results in resting inactivation.
What are subthreshold potentials?
changes in membrane potential that do not reach threshold. physiological examples include some synaptic potentials. in CNS, it is necessary for many excitatory synapses to be active simultaneously to generate a potential sufficient enough to reach threshold. Subthreshold potentials spread decrementally from their site of origin i.e the potential decreases progressively decreases with distance away from the origin
True or false: As an AP propagates down a neuron, the AP occurs at a different time for each location, but the amplitude and duration are the same at each location under normal circumstances.
True.