Action potentials

Action potentials are long-distance electrical signals (see Figure 4.2). These signals travel along the entire neuronal membrane. Unlike graded potentials in which the magnitude of the signal dissipates, the magnitude of the action potential is maintained throughout the length of the axon. Furthermore, in contrast to graded potentials whose magnitude is stimulus dependent, action potentials are always the same size. If a stimulus is strong enough to depolarize the membrane to a critical level referred to as threshold, then the membrane continues to depolarize on its own, independent of the stimulus. Typically, threshold is approximately 20 mV less negative than the resting membrane potential. Once threshold is reached, the continued depolarization takes place automatically. This is due to the diffusion of ions according to their concentration and electrical gradients and not due to the original stimulus itself.

Given that action potentials are always of a similar magnitude, how can stimuli of varied strengths be distinguished? A suprathreshold stimulus, one that is larger than necessary to depolarize the membrane simply to threshold, does not produce a larger action potential, but it does increase the frequency at which action potentials are generated. In other words, a stronger stimulus will trigger a greater number of action potentials per second.

The generation of an action potential involves changes in permeability to Na+ ions and K+ ions through voltage-gated ion channels. However, these permeability changes take place at slightly different times (see Figure 4.2). Voltage-gated ion channels open and close in response to changes in membrane potential. Initially, a stimulus will cause the membrane to depolarize

Time (msec)

Figure 4.2 The action potential. At the resting membrane potential (-70 mV), most ion channels are in their resting state — closed but capable of opening. When the neuron is stimulated and depolarized, the activation gates of the voltage-gated Na+ channels open, permitting the influx of Na+ ions and further depolarization toward threshold. At the threshold potential, all voltage-gated Na+ channels are open, resulting in the "spike" of the action potential. Approximately 1 msec after the activation gates open, the inactivation gates of the Na+ channels close; in addition, the activation gates of the K+ channels open, resulting in the repolarization of the neuron. The protracted increase in K+ ion permeability results in the after-hyperpolarization. It is during this time, when the membrane potential in the neuron is further away from threshold, that the cell is in its relative refractory period (RRP) and a larger than normal stimulus is needed to generate an action potential. The absolute refractory period (ARP) begins when the voltage-gated Na+ channels have become activated and continues through the inactivation phase. During this time, no further Na+ ion influx can take place and no new action potentials can be generated. Voltage-gated Na+ channels return to their resting state (activation gates closed, inactivation gates open) when the membrane potential approaches the resting membrane potential of the neuron.

toward threshold. When this occurs, voltage-gated Na+ channels begin to open. As a result, Na+ ions enter the cell down their concentration and electrical gradients. (Recall that, at this point, Na+ is in a greater concentration outside the cell and the inside of the cell is negative relative to the outside.).

The influx of Na+ ions causes further depolarization, resulting in the opening of more voltage-gated Na+ channels, continued influx of Na+ ions, and so on. This process continues until the membrane is depolarized to threshold at which point all of the Na+ channels are open and Na+ ion influx is rapid and abundant. At this time, the permeability to Na+ ions is approximately 600 times greater than normal. This ion flux causes the upward swing or spike of the action potential. During this phase of the action potential, the membrane reverses polarity because of the marked influx of (+) charges; the membrane potential at the peak of the action potential is +30 mV.

Approximately 1 msec after Na+ channels open, they close, thus preventing any further diffusion of (+) charges into the cell. At the same time, voltage-gated K+ channels open and K+ ions leave the cell down their concentration and electrical gradients. (At this point, K+ is not only in a greater concentration inside the cell, but the inside is also positive relative to the outside.). During this phase of the action potential, the permeability to K+ ions is approximately 300 times greater than normal. This efflux of (+) charges causes the membrane to repolarize back toward the resting membrane potential.

Sodium channels open more rapidly than K+ channels because they are more voltage sensitive and a small depolarization is sufficient to open them. Larger changes in membrane potential associated with further cell excitation are required to open the less voltage-sensitive K+ channels. Therefore, the increase in the permeability of K+ ions occurs later than that of Na+ ions. This is functionally significant because if both types of ion channels opened concurrently, the change in membrane potential that would occur due to Na+ ion influx would be cancelled out by K+ ion efflux and the action potential could not be generated.

To more fully understand the mechanism by which the action potential is generated, further explanation concerning the structure and activity of the voltage-gated ion channels is necessary. A voltage-gated Na+ channel has two different gates: the activation gate and the inactivation gate. At the resting membrane potential of -70 mV in an unstimulated neuron, the activation gate is closed and the permeability to Na+ ions is very low. In this resting state, the channel is closed but capable of opening in response to a stimulus. When stimulated by depolarization to threshold, the activation gates open very rapidly and Na+ ions diffuse into the cell causing the upward swing of the action potential. Once these activation gates open, the inactivation gates begin to close, although these gates close more slowly. At the peak of the action potential when the inactivation gates are now closed, these channels are no longer permeable to Na+ ions and incapable of opening regardless of further stimulation.

Therefore, Na+ channels cannot reopen, Na+ ions cannot enter the cell, and another action potential cannot be generated. In fact, these voltage-gated channels cannot return to their resting position and become capable of opening until the neuron has first repolarized to -70 mV from the existing action potential. This period of time — beginning when all the Na+ channels are open and lasting through their inactivation phase — is referred to as the absolute refractory period. Regardless of the strength of the stimulus, no new action potentials can be generated. The approximately 2-msec length of this period limits the number of action potentials that neurons can generate to up to 500 per second.

The voltage-gated K+ channel has only one gate, which is typically closed at the resting membrane potential. This gate also opens in response to depolarization of the membrane toward zero. However, unlike the activation gate of the voltage-gated Na+ channel that opens very quickly, this gate opens very slowly so that the permeability to K+ ions is delayed. In fact, it opens at approximately the same time that the inactivation gates in the Na+ channels close. Therefore, Na+ ion permeability decreases and K+ ion permeability increases simultaneously, resulting in the outward movement of (+) charges and rapid repolarization.

Voltage-gated K+ channels open and close slowly; therefore, the increase in permeability to K+ ions is prolonged. As a result, K+ ions continue to exit the cell and the membrane potential approaches the equilibrium potential for potassium. This phase of the action potential is referred to as after-hyper-polarization. Because the membrane potential is now further away from threshold, a larger than normal stimulus is necessary to cause depolarization to threshold. During this phase of hyperpolarization it is possible, but more difficult, for the neuron to generate another action potential. This relative refractory period lasts from the end of the absolute refractory period until the voltage-gated K+ channels have returned to their resting state and the membrane once again returns to its resting potential.

During the course of the action potential, Na+ ions entered the cell and K+ ions exited it. In order to prevent eventual dissipation of the concentration gradients for Na+ and K+ ions across the cell membrane over time, these substances must be returned to their original positions. The slow but continuous activity of the Na+-K+ pump is responsible for this function and returns Na+ ions to the extracellular fluid and K+ ions to the intracellular fluid.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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