brane potential to change after a stimulus is applied is called the time constant or t, and its relationship to capacitance (C) and resistance (R) is defined by the following equation:
In the absence of an action potential, a stimulus applied to the neuronal membrane results in a local potential change that decreases with distance away from the point of stimulation. The voltage change at any point is a function of current and resistance as defined by Ohm's law. If a lig-and-gated channel opens briefly and allows positive ions to enter the neuron, the electrical potential derived from that current will be greatest near the channels that opened, and the voltage change will steadily decline with increasing distance away from that point. The reason for the decline in voltage change with distance is that some of the ions back-leak out of the membrane because it is not a perfect insulator, and less charge reaches more distant sites. Since membrane resistance is a stable property of the membrane, the diminished current with distance away from the source results in a diminished voltage change. The distance at which the initial transmembrane voltage change has fallen to 37% of its peak value is defined as the space constant or X. The value of the space constant depends on the internal axo-plasmic resistance (Ra) and on the transmembrane resistance (Rm) as defined by the following equation:
Rm is usually measured in ohm-cm and Ra in ohm/cm. Ra decreases with increasing diameter of the axon or dendrite; thus, more current will flow farther along inside the cell, and the space constant is larger. Similarly, if Rm increases, less current leaks out and the space constant is larger. The larger the space constant, the farther along the membrane a voltage change is observed after a local stimulus is applied.
Membrane capacitance and resistance, and the resultant time and space constants, play an important role in both the propagation of the action potential and the integration of incoming information.
An Action Potential Is Generated at the Axon Hillock and Conducted Along the Axon
An action potential depends on the presence of voltage-gated sodium and potassium channels that open when the neuronal membrane is depolarized. These voltage-gated channels are restricted to the axon of most neurons. Thus, neuronal dendrites and cell bodies do not conduct action potentials. In most neurons, the axon hillock of the axon has a very high density of these voltage-gated channels. This region is also known as the trigger zone for the action potential. In sensory neurons that convey information to the CNS from distant peripheral targets, the trigger zone is in the region of the axon close to the peripheral target.
When the axon is depolarized slightly, some voltage-gated sodium channels open; as Na+ ions enter and cause more depolarization, more of these channels open. At a critical membrane potential called the threshold, incoming Na+ exceeds outgoing K+ (through leakage channels), and the resulting explosive opening of the remaining voltage-
gated sodium channels initiates an action potential. The action potential then propagates to the axon terminal, where the associated depolarization causes the release of neuro-transmitter. The initial depolarization to start this process derives from synaptic inputs causing ligand-gated channels to open on the dendrites and somata of most neurons. For peripheral sensory neurons, the initial depolarization results from a generator potential initiated by a variety of sensory receptor mechanisms (see Chapter 4).
Characteristics of the Action Potential. Depolarization of the axon hillock to threshold results in the generation and propagation of an action potential. The action potential is a transient change in the membrane potential characterized by a gradual depolarization to threshold, a rapid rising phase, an overshoot, and a repolarization phase. The repolarization phase is followed by a brief afterhyperpolar-ization (undershoot) before the membrane potential again reaches resting level (Fig. 3.4A).
kThe phases of an action potential. A, Depolarization to threshold, the rising phase, overshoot, peak, repolarization, afterhyperpolarization, and return to the resting membrane potential. B, Changes in sodium (gNa) and potassium (gK) conductances associated with an action potential. The rising phase of the action potential is the result of an increase in sodium conductance, while the repolarization phase is a result of a decrease in sodium conductance and a delayed increase in potassium conductance.
The action potential may be recorded by placing a mi-croelectrode inside a nerve cell or its axon. The voltage measured is compared to that detected by a reference electrode placed outside the cell. The difference between the two measurements is a measure of the membrane potential. This technique is used to monitor the membrane potential at rest, as well as during an action potential.
Action Potential Gating Mechanisms. The depolarizing and repolarizing phases of the action potential can be explained by relative changes in membrane conductance (permeability) to sodium and potassium. During the rising phase, the nerve cell membrane becomes more permeable to sodium,- as a consequence, the membrane potential begins to shift more toward the equilibrium potential for sodium. However, before the membrane potential reaches ENa, sodium permeability begins to decrease and potassium permeability increases. This change in membrane conductance again drives the membrane potential toward EK, accounting for repolarization of the membrane (Fig. 3.4B).
The action potential can also be viewed in terms of the flow of charged ions through selective ion channels. These voltage-gated channels are closed when the neuron is at rest (Fig. 3.5A). When the membrane is depolarized, these channels begin to open. The Na+ channel quickly opens its activation gate and allows Na+ ions to flow into the cell (Fig. 3.5B). The influx of positively charged Na+ ions causes the membrane to depolarize. In fact, the membrane potential actually reverses, with the inside becoming positive,- this is called the overshoot. In the initial stage of the action potential, more Na+ than K+ channels are opened because the K+ channels open more slowly in response to depolarization. This increase in Na+ permeability compared to that of K+ causes the membrane potential to move toward the equilibrium potential for Na+.
At the peak of the action potential, the sodium conductance begins to fall as an inactivation gate closes. Also, more K+ channels open, allowing more positively charged K+ ions to leave the neuron. The net effect of inactivating Na+ channels and opening additional K+ channels is the repolarization of the membrane (Fig. 3.5C).
As the membrane continues to repolarize, the membrane potential becomes more negative than its resting level. This afterhyperpolarization is a result of K+ channels remaining open, allowing the continued efflux of K+ ions. Another way to think about afterhyperpolarization is that the membrane's permeability to K+ is higher than when the neuron is at rest. Consequently, the membrane potential is driven even more toward the K+ equilibrium potential (Fig. 3.5D).
The changes in membrane potential during an action potential result from selective alterations in membrane conductance (see Fig. 3.4B). These membrane conductance changes reflect the summated activity of individual voltage-gated sodium and potassium ion channels. From the temporal relationship of the action potential and the membrane conductance changes, the depolarization and rising phase of the action potential can be attributed to the increase in sodium ion conductance, the repolarization phases to both the decrease in sodium conductance and the increase in potassium conductance, and afterhyperpolariza-tion to the sustained increase of potassium conductance.
Alterations in voltage-gated sodium and potassium channels, as well as in voltage-gated calcium and chloride channels, are now known to be the basis of several diseases of nerve and muscle. These diseases are collectively known as channelopathies (see Clinical Focus Box 3.1).
Initiation of the Action Potential. In most neurons, the axon hillock (initial segment) is the trigger zone that generates the action potential. The membrane of the initial segment contains a high density of voltage-gated sodium and potassium ion channels. When the membrane of the initial segment is depolarized, voltage-gated sodium channels are opened, permitting an influx of sodium ions. The influx of these positively charged ions further depolarizes the membrane, leading to the opening of other voltage-gated sodium channels. This cycle of membrane depolarization, sodium channel activation, sodium ion influx, and membrane depolarization is an example of positive feedback, a regenerative process (Fig. 1.3) that results in the explosive activation of many sodium ion channels when the threshold membrane potential is reached. If the depolarization of the initial segment does not reach threshold, then not enough sodium channels are activated to initiate the regenerative process. The initiation of an action potential is, therefore, an "all-or-none" event; it is generated completely or not at all.
Propagation and Speed of the Action Potential. After an action potential is generated, it propagates along the axon toward the axon terminal; it is conducted along the axon with no decrement in amplitude. The mode in which action potentials propagate and the speed with which they are conducted along an axon depend on whether the axon is myelinated. The diameter of the axon also influences the speed of action potential conduction: larger-diameter axons have faster action potential conduction velocities than smaller-diameter axons.
In unmyelinated axons, voltage-gated Na+ and K+ channels are distributed uniformly along the length of the axonal membrane. An action potential is generated when the axon hillock is depolarized by the passive spread of synaptic potentials along the somatic and dendritic membrane (see below). The hillock acts as a "sink" where Na+ ions enter the cell. The "source" of these Na+ ions is the extracellular space along the length of the axon. The entry of Na+ ions into the axon hillock causes the adjacent region of the axon to depolarize as the ions that entered the cell, during the peak of the action potential, flow away from the sink. This local spread of the current depolarizes the adjacent region to threshold and causes an action potential in that region. By sequentially depolarizing adjacent segments of the axon, the action potential propagates or moves along the length of the axon from point to point, like a traveling wave (Fig. 3.6A).
Just as large-diameter tubes allow a greater flow of water than small-diameter tubes because of their decreased resistance, large-diameter axons have less cytoplasmic resistance, thereby permitting a greater flow of ions. This increase in ion flow in the cytoplasm causes greater lengths of the axon to be depolarized, decreasing the time needed for the action potential to travel along the axon. Recall
Was this article helpful?
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.