Neuronal Action Potential -
In the lecture on the resting membrane potential
, we learned how the membrane potential (Vm
) is established. We also learned about the factors that govern the value of the membrane potential. You recall that in most cells, the resting membrane potential is governed by the relative permeability to potassium (K+
), sodium (Na+
), and chloride (Cl-
) ions. In fact, in a typical neuron at rest, the relative permeabilites values are approximately 1 : 0.05 : 0.45 (pK
). We also mentioned that the relative permeability to a given ion is a function of the number of channels specific for that ion that are open. The resting membrane potential in a typical neuron is near −70 mV. Therefore, because at rest pK
is greater than either pNa
, the resting membrane potential in most cells is close to the equilibrium potential for K+
≈ −90 mV). We used the Nernst equation
to determine the equilibrium potential for any given ion, and we used the Goldman-Hodgkin-Katz (GHK)
equation to determine the resting membrane potential in cells. In this lecture, we will see that rapid changes in permeability to Na+
ions are responsible for electrical impulses generated by neurons. The resulting electrical impulses, in turn, form the basis for information transmission in the nervous system. As we will in this lecture, the changes in Na+
permeability are due to the opening of voltage-gated Na+
channels and voltage-gated K+
Figure 1. A typical neuronal action potential.
A neuronal action potential is a rapid reversal of the membrane potential brought about by rapid changes in plasma membrane permeability to Na+ and K+. VNa and VK are the equilibrium potentials for Na+ and K+, respectively. See text for details.
Now that we understand the mechanisms responsible for the generation and manipulation of the membrane potential, we can tackle the question of how cells of the nervous system (in particular neurons) generate nervous impulses. Nervous impulses are the electrical signals by which neurons talk to one another and also to other cells of the body. The nervous impulse is referred to as the action potential. An action potential is a brief reversal of the membrane potential (Fig. 1). At rest, the Vm of a neuron is around −70 mV (close to VK), but during an action potential, Vm transiently approaches +50 mV (close to VNa). The Vm then rapidly returns to the resting potential and even briefly goes beyond the resting potential to approach VK before finally returning to the resting value of about −70 mV. The entire process takes about 3-5 ms. This potential reversal of more than 100 mV is responsible for electrical signaling in the nervous system, and is the basis of information transmission in the nervous system. In this lecture, we will learn the mechanisms that give rise to the action potential. In the next lecture, we will see how this electrical signal can travel along axonal projections of neurons to reach other neurons, or other cells in the body.
To understand the uniqueness of neurons as excitable cells, we can examine the response of non-excitable cells to artificial electrical stimulation (Fig. 2) and compare this response to that of excitable cells such as neurons (Fig. 3). Recall from the lecture on the resting membrane potential
that we can impale a cell with a glass microelectrode. The microelectrode could then be used to inject positive or negative charge into the cell. The applied electrical stimuli are in general in the form of square-wave pulses
, in that at a given point in time a predefined amount of charge is introduced into the cell and maintained until the end of the pulse. Introduction of positive charge into the cell leads to membrane depolarization, and introduction of negative charge into the cell leads to membrane hyperpolarization.
Figure 2. Electrical stimulation of non-excitable cells.
In non-excitable cells, both hyperpolarizing and depolarizing electrical stimulation result in graded potentials that are proportional in magnitude to the amplitude of the pulse. The upper trace (red) shows the square-wave pulses applied to a cell, and the bottom trace (blue) shows the membrane potential of the cell being stimulated. The two traces are on the same time scale. Hyperpolarizing stimuli lead to membrane hyperpolarization, and depolarizing stimuli lead to membrane depolarization.
In non-excitable cells, depolarizing or hyperpolarizing stimulation only temporarily alters the membrane potential, but does not lead to "excitation" of the cell (Fig. 2). At the end of the depolarizing or hyperpolarizing pulse, the membrane potential simply returns to the resting value. This behavior is independent of the strength of the stimuli. The amplitude of the depolarization or hyperpolarization is directly proportional to the amplitude of the stimulus; the larger the amplitude of the stimulus, the larger the change in the membrane potential. These changes in the membrane potential are referred to as graded potentials because they are proportional to the magnitude of the stimulus (Fig. 2). These graded potentials represent the passive property of the membrane to electrical stimulation. It is interesting that the electrical properties of biological membranes can be modeled by the membrane equivalent circuit, which is represented by a capacitor and a resistor in parallel. The passive property of the membrane resembles that of such a circuit and can be understood strictly based on the properties of capacitors and resistors.
In excitable cells, hyperpolarizing stimuli lead to the same graded responses that are seen in non-excitable cells (Fig. 3). However, the nature of the response of excitable cells to depolarizing stimuli depends on the strength of the applied stimulus. If weak stimuli are given, the response is graded and is similar to that of a non-excitable cell (Fig. 3). If, however, a strong enough stimulus is given such that the resulting depolarization surpasses a certain critical voltage, an action potential is generated. The voltage that must be surpassed in order to get an action potential is referred to as threshold
. In most neurons threshold is around −40 to −50 mV. If a stimulus leads to a membrane depolarization that is more negative than the threshold value, the stimulus is said to be sub-threshold
. Sub-threshold stimuli do not lead to action potentials. If the stimulus leads to a membrane depolarization that is less negative (more positive) than the threshold value, it is said to be supra-threshold
. In general, supra-threshold stimuli lead to action potentials. This is almost always true if the supra-threshold stimulus is applied to a neuron at rest (i.e., a neuron that is not undergoing excitation). However, if a neuron is undergoing excitation, there are times when even supra-threshold stimuli do not lead to excitation of neurons. This is because during excitation, there is a period during which the neuron is refractory to subsequent stimulation (see Refractory Periods
). In this lecture, we will consider these scenarios in detail.
Figure 3. Electrical stimulation of neurons.
In excitable cells such as neurons, hyperpolarizing electrical stimulation results in hyperpolarizing graded potentials that are proportional in magnitude to the amplitude of the pulse. Sub-threshold depolarizing stimuli cause graded potentials, but supra-threshold depolarizing stimuli elicit all-or-nothing action potentials. The upper trace (red) shows the square-wave pulses applied to a neuron, and the bottom trace (blue) shows the membrane potential of the neuron being stimulated. The two traces are on the same time scale. The dashed line represents the threshold voltage (Vthreshold) of approximately −50 mV.
It is important to note that while in this lecture we discuss artificial electrical stimulation of neurons, physiologically, neurons become stimulated by other neurons or by environmental stimuli (in the case of sensory receptors). The mechanisms by which neurons become stimulated under physiological conditions will be discussed later when we consider how electrical information is transmitted from one neuron to another neuron (see Neuronal Signaling: Synaptic Neurotransmission). Nevertheless, once a neuron is stimulated such that its membrane potential reaches threshold, a neuronal action potential will be generated. Thus, whether a neuron is stimulated by another neuron or artificially by an intracellular microelectrode, the resulting action potential will be the same. Therefore, electrophysiological stimulation of neurons provides a reliable and convenient method by which to study neuronal physiology.
Posted: Thursday, July 5, 2012