Voltage-sensitive channels in the membrane are responsible for allowing the entry of Na+ ions, driven by their electrochemical gradient. This entry of positive charge enhances depolarization and is referred to as a local response. Unlike a passive electrotonic response, the local response involves active changes in membrane properties, specifically its Na+ conductance. However, the local response is not self-regenerating and decreases in amplitude with distance. It is not sufficient to generate an action potential.

When the depolarizing current pulse exceeds a certain threshold membrane potential (typically around -55 mV), it triggers an action potential. The shape of an action potential is shown in Fig. 5.4. When the membrane is depolarized past threshold, the depolarization becomes explosive and the membrane potential reverses from negative to positive but does not reach the Nernst equilibrium potential for Na+ (ENa). The membrane potential then rapidly repolarizes back towards the resting membrane potential and often hyperpolarizes beyond it, resulting in an afterhyperpolarization. The main phase of the action potential typically lasts for 1 to 2 msec, while the afterhyperpolarization can persist for a few to 100 msec depending on the type of neuron.

The action potential differs from subthreshold and passive responses in three important ways: (1) It has a much larger amplitude, with the membrane potential overshooting 0 mV. (2) It is propagated down the entire length of the axon without decrement, as it is regenerated along the axon. (3) It is an all-or-none response, meaning that a stimulus either produces a full-sized action potential or fails to produce one. This is in contrast to the graded nature of passive and local responses, as well as synaptic responses.

The resting membrane potential is primarily determined by the weighted average of the Nernst potentials for Na+ (ENa) and K+ (EK). The conductance to each ion, represented by g = 1/resistance, determines the weighting factors. At rest, the conductance to K+ (gK) is higher than that for Na+ (gNa), resulting in a resting membrane potential (Vr) close to EK (Vr ≅ -70 mV). However, changes in the relative conductances to these ions can alter the membrane potential. For example, an increase in gK hyperpolarizes the membrane, while a decrease in gK depolarizes the membrane. Similarly, an increase in gNa depolarizes the membrane and can even lead to a reversal in membrane polarity if of sufficient magnitude, as ENa is approximately +65 mV.
Fig. 5.1B ). Opening of these voltage-sensitive channels changes the membrane’s resistance and allows Na+ to enter more easily, driven by its electrochemical gradient. This entry of positive charge (Na+ current) enhances the depolarization by adding to the current pulse delivered by the electrode. The resulting depolarization is called a local response. The local response results from active changes in membrane properties (specifically, its Na+ conductance), whereas in a passive electrotonic response, the conductance to various ions remains constant. Nevertheless, the local response is not self-regenerating but, again, decreases in amplitude with distance. The change in membrane properties is insufficient for what is needed to generate an action potential.
Suprathreshold Response: The Action Potential
Local responses will increase in size as the amplitude of the depolarizing current pulse is increased, until the threshold membrane potential is reached, at which point a different sort of response, the action potential (or spike), can occur. The threshold value is typically near −55 mV. Normally, when the membrane potential exceeds this value, an action potential is always triggered.
Fig. 5.4 shows the typical shape of an action potential. When the membrane is depolarized past threshold, the depolarization becomes explosive and overshoots in such a way that the membrane potential reverses from negative to positive and approaches, but does not reach, the Nernst equilibrium potential for Na+ (ENa; see ). The membrane potential then returns toward the resting membrane potential (repolarizes) almost as rapidly as it was depolarized, and in general, it hyperpolarizes beyond its resting potential (the afterhyperpolarization). The main phase of the action potential (from the onset to the return to the resting potential) typically has a duration of 1 to 2 msec, but the afterhyperpolarization, it can persist •Fig. 5.4 Components of the Action Potential With Regard to Time and Voltage. Markersindicatetheabsoluteandrelativerefractoryperiods.Notethatthetimescaleforthefirstfewmillisecondshasbeenexpandedforclarity.RMP,restingmembranepotential.(RedrawnfromBlankenshipJ.Neurophysiology. Philadelphia:Mosby;2002.) from a few to 100 msec, depending on the particular type of neuron.
The action potential differs from the subthreshold and passive responses in three important ways: (1) It is a response of much larger amplitude, in which the polarity of the membrane potential actually overshoots 0 mV (the cell interior becomes positive in relation to the exterior).
(2) The action potential is generally propagated down the entire length of the axon without decrement (i.e., it maintains its size and shape because it is regenerated as it travels along the axon). (3) It is an all-or-none response, which means that a stimulus normally either produces a full-sized action potential or fails to produce one. This all-or-none nature is in contrast both to the graded nature of the passive and local responses described previously and to synaptic responses (see
Ionic Basis of Action Potentials
Recall that the resting membrane potential is determined primarily by the weighted average of the Nernst potentials for Na+ (ENa) and K+ (EK), as defined by the chord conductance equation (see ). The weighting factors are the conductance (g = 1/resistance) to each ion. At rest the conductance to K+ (gK) is high in relation to that for Na+ (gNa), and so the resting membrane potential (Vr) is closer to EK (Vr ≅−70 mV). If, however, the relative conductances to these ions were to change, this would cause a corresponding change in the membrane potential. For example, an increase in gK would hyperpolarize the membrane, whereas a decrease in gK would depolarize the membrane because EK is approximately −100 mV. Conversely, an increase in gNa would depolarize the membrane and, if of sufficient magnitude, even a lead to reversal in membrane polarity because ENa is approximately +65 mV.