## Absolute and Relative Refractory Periods

The absolute refractory period refers to that period of time after the initiation of one action potential when it is impossible to initiate another action potential no matter what the stimulus intensity used. The relative refractory period refers to that period of time after the initiation of one action potential when it is possible to initiate another action potential but only with a stimulus intensity greater than that used to produce the first action potential. At least part of the relative refractory period can be explained by the hyperpolarizing afterpotential. Assume that a cell has a resting potential of —60 mV and a threshold of —45 mV. If the cell is depolarized by 15 mV to reach threshold, an all-or-nothing action potential will be initiated, followed by the associated repolarization phase and the hyperpolar-izing afterpotential. What happens if one attempts to initiate a second action potential during the undershoot? Initially, the cell was depolarized by 15 mV (from —60 to —45 mV) to reach threshold. However, if the same depolarization (15 mV) is delivered during some phase of the hyperpolarizing afterpotential, the 15 mV depolarization would fail to reach threshold (—45 mV) and would be insufficient to initiate an action potential. If, however, the cell is depolarized by more than 15 mV, threshold can again be reached and another action potential initiated. Eventually, the hyperpolarizing afterpotential would terminate, and the original 15-mV stimulus would again be sufficient to reach threshold. The process of Na+ inactivation also contributes to the relative refractory period (see below).

### 4. Resting and Action Potentials in Excitable Cells

The absolute refractory period refers to that period of time after an action potential when it is impossible to initiate a new action potential no matter how large the stimulus. This is a relatively short period of time that varies from cell to cell but roughly occurs approximately 1/2 to 1 msec after the peak of the action potential. To understand the absolute refractory period, it is necessary to understand Na+ inactivation in greater detail. In Fig. 19, a membrane initially at a potential of —60 mV is voltage clamped to a new value of 0 mV (pulse 1, Fig. 19A). With depolarization, there is a rapid increase in Na+ permeability, followed by its spontaneous decay. When this first pulse is followed by an identical pulse (pulse 2) to the same level of membrane potential soon thereafter (Fig. 19B), there is still an increase in Na+ permeability, but the increase is much smaller than it was for the first stimulus. Indeed, when the separation between these pulses is reduced further, a point is reached where there is absolutely no change in Na+ permeability produced by the second depolarization (Fig. 19C). The two pulses must be separated by several milliseconds before the change in Na+ permeability is equal to that obtained initially (Fig. 19A). How do we explain these results, and what do they have to do with the absolute refractory period? Just as it takes a certain amount of time for the Na+ channels to inactivate, it also takes some time for these channels to recover from the inactivation and be able to respond again to a second depolarization. Therefore, as a result of initiating