The electrical events in neuronal excitation have been studied especially in the large motor neurons of the anterior horns of the spinal cord. Therefore, the events described in the next few sections pertain essentially to these neurons. Except for quantitative differences, they apply to most other neurons of the nervous system as well.
Resting Membrane Potential of the Neuronal Soma. Figure 1 shows the soma of a spinal motor neuron, indicating a resting membrane potential of about −65 millivolts. This resting membrane potential is somewhat less negative than the −90 millivolts found in large peripheral nerve fibers and in skeletal muscle fibers; the lower voltage is important because it allows both positive and negative control of the degree of excitability of the neuron. That is, decreasing the voltage to a less negative value makes the membrane of the neuron more excitable, whereas increasing this voltage to a more negative value makes the neuron less excitable. This mechanism is the basis for the two modes of function of the neuron— either excitation or inhibition—as explained in the next sections.
Fig1. Distribution of sodium, potassium, and chloride ions across the neuronal somal membrane; origin of the intrasomal membrane potential.
Concentration Differences of Ions Across the Neuronal Somal Membrane. Figure 1 also shows the concentration differences across the neuronal somal membrane of the three ions that are most important for neuronal function: sodium ions, potassium ions, and chloride ions. At the top, the sodium ion concentration is shown to be high in the extracellular fluid (142 mEq/L) but low inside the neuron (14 mEq/L). This sodium con centration gradient is caused by a strong somal membrane sodium pump that continually pumps sodium out of the neuron.
Figure 41 also shows that potassium ion concentra tion is high inside the neuronal soma (120 mEq/L) but low in the extracellular fluid (4.5 mEq/L). Furthermore, it shows that there is a potassium pump (the other half of the Na+K+ pump) that pumps potassium to the interior.
figure 1 shows the chloride ion to be of high con centration in the extracellular fluid but of low concentration inside the neuron. The membrane may be somewhat permeable to chloride ions, and there may be a weak chloride pump. Yet, most of the reason for the low concentration of chloride ions inside the neuron is the −65 millivolts in the neuron. That is, this negative voltage repels the negatively charged chloride ions, forcing them outward through channels until the concentration is much less inside the membrane than outside.
Let us recall from Chapters 4 and 5 that an electrical potential across the cell membrane can oppose movement of ions through a membrane if the potential is of proper polarity and magnitude. A potential that exactly opposes movement of an ion is called the Nernst potential for that ion, which is represented by the following equation:
where EMF is the Nernst potential in millivolts on the inside of the membrane. The potential will be negative (−) for positive ions and positive (+) for negative ions.
Now let us calculate the Nernst potential that will exactly oppose the movement of each of the three separate ions: sodium, potassium, and chloride.
For the sodium concentration difference shown in Figure 1 (142 mEq/L on the exterior and 14 mEq/L on the interior), the membrane potential that will exactly oppose sodium ion movement through the sodium channels calculates to be +61 millivolts. However, the actual membrane potential is −65 millivolts, not +61 millivolts. Therefore, the sodium ions that leak to the interior are immediately pumped back to the exterior by the sodium pump, thus maintaining the −65 millivolt negative potential inside the neuron.
For potassium ions, the concentration gradient is 120 mEq/L inside the neuron and 4.5 mEq/L outside. This concentration gradient calculates to be a Nernst potential of −86 millivolts inside the neuron, which is more negative than the −65 that actually exists. Therefore, because of the high intracellular potassium ion concentration, there is a net tendency for potassium ions to diffuse to the outside of the neuron, but this action is opposed by continual pumping of these potassium ions back to the interior.
Finally, the chloride ion gradient, 107 mEq/L outside and 8 mEq/L inside, yields a Nernst potential of −70 millivolts inside the neuron, which is only slightly more negative than the actual measured value of −65 millivolts. Therefore, chloride ions tend to leak very slightly to the interior of the neuron, but those few that do leak are moved back to the exterior, perhaps by an active chloride pump.
Keep these three Nernst potentials in mind and remember the direction in which the different ions tend to diffuse, because this information is important in understanding both excitation and inhibition of the neuron by synapse activation or inactivation of ion channels.
Uniform Distribution of Electrical Potential Inside the Soma. The interior of the neuronal soma contains a highly conductive electrolytic solution, the intracellular fluid of the neuron. Furthermore, the diameter of the neuronal soma is large (from 10 to 80 micrometers), causing almost no resistance to conduction of electric current from one part of the somal interior to another part. Therefore, any change in potential in any part of the intrasomal fluid causes an almost exactly equal change in potential at all other points inside the soma (i.e., as long as the neuron is not transmitting an action potential). This principle is important because it plays a major role in “summation” of signals entering the neuron from multiple sources.
Effect of Synaptic Excitation on the Postsynaptic Membrane—Excitatory Postsynaptic Potential. Figure 2A shows the resting neuron with an unexcited presynaptic terminal resting on its surface. The resting membrane potential everywhere in the soma is −65 millivolts.
Fig2. Three states of a neuron. A, Resting neuron, with a normal intraneuronal potential of −65 millivolts. B, Neuron in an excited state, with a less negative intraneuronal potential (−45 millivolts) caused by sodium influx. C, Neuron in an inhibited state, with a more negative intraneuronal membrane potential (−70 millivolts) caused by potassium ion efflux, chloride ion influx, or both.
Figure 2B shows a presynaptic terminal that has secreted an excitatory transmitter into the cleft between the terminal and the neuronal somal membrane. This transmitter acts on the membrane excitatory receptor to increase the membrane’s permeability to Na+. Because of the large sodium concentration gradient and large electrical negativity inside the neuron, sodium ions diffuse rapidly to the inside of the membrane.
The rapid influx of positively charged sodium ions to the interior neutralizes part of the negativity of the resting membrane potential. Thus, in Figure 2B, the resting membrane potential has increased in the positive direction from −65 to −45 millivolts. This positive increase in voltage above the normal resting neuronal potential— that is, to a less negative value—is called the excitatory postsynaptic potential (or EPSP), because if this potential rises high enough in the positive direction, it will elicit an action potential in the postsynaptic neuron, thus exciting it. (In this case, the EPSP is +20 millivolts—i.e., 20 milli volts more positive than the resting value.)
Discharge of a single presynaptic terminal can never increase the neuronal potential from −65 millivolts all the way up to −45 millivolts. An increase of this magnitude requires simultaneous discharge of many terminals— about 40 to 80 for the usual anterior motor neuron—at the same time or in rapid succession. This simultaneous discharge occurs by a process called summation, which is discussed in the next sections.
Generation of Action Potentials in the Initial Segment of the Axon Leaving the Neuron—Threshold for Excitation. When the EPSP rises high enough in the positive direction, there comes a point at which this rise initiates an action potential in the neuron. However, the action potential does not begin adjacent to the excitatory synapses. Instead, it begins in the initial segment of the axon where the axon leaves the neuronal soma. The main reason for this point of origin of the action potential is that the soma has relatively few voltage gated sodium channels in its membrane, which makes it difficult for the EPSP to open the required number of sodium channels to elicit an action potential. Conversely, the membrane of the initial segment has seven times as great a concentration of voltage-gated sodium channels as does the soma and, therefore, can generate an action potential with much greater ease than can the soma. The EPSP that will elicit an action potential in the axon initial segment is between +10 and +20 milli volts, in contrast to the +30 or +40 millivolts or more required on the soma.
Once the action potential begins, it travels peripherally along the axon and usually also backward over the soma. In some instances it travels backward into the dendrites but not into all of them because they, like the neuronal soma, have very few voltage-gated sodium channels and therefore frequently cannot generate action potentials at all. Thus, in Figure 2B, the threshold for excitation of the neuron is shown to be about −45 millivolts, which represents an EPSP of +20 millivolts—that is, 20 millivolts more positive than the normal resting neuronal potential of −65 millivolts.
