Neuronal Action Potential -
As mentioned in the last section
, opening of the Na+
channels, spontaneously and rapidly leads to their inactivation. At the peak of the action potential, all Na+
channels become inactivated. When Na+
channels are inactivated, they cannot be immediately opened again (see figure
channel inactivation). Recovery from inactivation is a time- and voltage-dependent process, and full recovery usually takes about 3-4 ms. Therefore, it takes about 3-4 ms for all Na+
channels to come out of inactivation in order to be ready for activation (opening) again. The period from the initiation of the action potential to immediately after the peak is referred to as the absolute refractory period (ARP)
(see Figs. 1 and 2). This is the time during which another stimulus given to the neuron (no matter how strong) will not lead to a second action potential. Thus, because Na+
channels are inactivated during this time, additional depolarizing stimuli do not lead to new action potentials. The absolute refractory period takes about 1-2 ms.
Figure 1. Absolute and relative refractory periods.
During the absolute refractory period, a second stimulus (no matter how strong) will not excite the neuron. During the relative refractory period, a stronger than normal stimulus is needed to elicit neuronal excitation.
After the absolute refractory period, Na+
channels begin to recover from inactivation and if strong enough stimuli are given to the neuron, it may respond again by generating action potentials. However, during this time, the stimuli given must be stronger than was originally needed when the neuron was at rest. This situation will continue until all Na+
channels have come out of inactivation. The period during which a stronger than normal stimulus is needed in order to elicit an action potential is referred to as the relative refractory period (RRP)
. During the relative refractory period, since pK
remains above its resting value (see figure
on timecourse of pK
during the action potential), continued K+
flow out of the cell would tend to oppose any depolarization caused by opening of Na+
channels that have recovered from inactivation.
Considering the excitability of the neuron following an action potential, it can be seen that the neuron is not excitable at all during the absolute refractory period, however, neuronal excitability recovers in a time-dependent (and also voltage-dependent) manner follwoing the absolute refractory period (Fig. 2). As mentioned above, the period immediately following the absolute refractory period until neuronal excitability is similar to that for a resting neuron is the relative refractory period. If the neuron is stimulated with a stimulus strong enough only to bring a resting neuron to threshold, the neuron will only respond when the relative refractory period is over (i.e., the neuron is back to its resting state). Howerver, during the relative refractory period, the neuron can be excited if a stronger than normal stimulus is applied. The strength of the stimulus needed to excite the neuron during the relative refractory period is very high initially immediately following the end of the absolute refractory period, but decreases throughout the relative refractory period until it reaches that needed to excite a neuorn at rest (i.e., at the end of the relative refractory period (Fig. 3).
Figure 2. Recovery of neuronal excitability.
During the absolute refractory period, the neuron cannot be excited to generate a second action potential (no matter how intense the stimulus). As Na+ channels begin to recover from inactivation, excitability is gradually restored. This recovery period is the relative refractory period during which a stronger than normal stimulus is needed to initiate a new action potential.
Figure 3. Threshold stimulus strength required to elicit an action potential during the relative reftractory period.
No stimulus, no matter how strong, will bring the neuron to threshold during the absolute refractory period. During the relative refractory period, the neuron can be excited with stimuli stronger than that needed to bring a resting neuron to threshold. The strength of of the stimulus required is very high early in the relative refractory period and gradually becomes smaller throughout the relative refractory period as Na+
channels recover from inactivation and as K+
permeability returns to its resting level (see figure
). At the end of the relative refractory period, when the neuron is back to its resting state, the stimulus strength is at the minimum level required to bring a resting neuron to threshold (dashed line).
In summary, inactivation of Na+ channels is solely responsible for the absolute refractory period. Both Na+ channel inactivation and the greater than resting pK value are responsible for the relative refractory period.
The absolute refractory period is responsible for setting the upper limit on the maximum number of action potentials that can be generated during any given time period. In other words, the absolute refractory period determines the maximum frequency of action potentials that can be generated at any point along the axon plasma membrane. This action potential frequency, in turn, has important physiological implications for how the nervous system can respond to high-frequency stimuli, and also for the ability of the nervous system to send high-frequency signals to effector organs when needed (see Frequency Coding in the Nervous System
One final note about the refractory period is in order. As mentioned before, the numbers reported in these lectures for various physiological processes correspond to what has been established to be the "norm" or the best-studied example of the process. Although we have reported the refractory period to be 3-4 ms long, it should be noted that the hyperpolarization phase can last up to 15 ms in some neurons. In these neurons, therefore, the relative refractory period is much longer.
Posted: Thursday, July 5, 2012