The resting membrane potential of large nerve ﬁbers when not transmitting nerve signals is about –90 millivolts. That is, the potential inside the ﬁber is 90 millivolts more negative than the potential in the extracellular ﬂuid on the outside of the ﬁber. In the next few paragraphs, we explain all the factors that determine the level of this resting potential, but before doing so, we must describe the transport properties of the resting nerve membrane for sodium and potassium.
Active Transport of Sodium and Potassium Ions through the Membrane—the Sodium-Potassium (Na+ -K+) Pump. First, let us recall that all cell membranes of the body have a powerful Na+ -K+ that continually pumps sodium ions to the outside of the cell and potassium ions to the inside, as illustrated on the left-hand side in. Further, note that this is an electrogenic pump because more positive charges are pumped to the outside than to the inside (three Na+ ions to the outside for each two K+ ions to the inside), leaving a net deﬁcit of positive ions on the inside; this causes a negative potential inside the cell membrane The Na+ -K+ also causes large concentration gradients for sodium and potassium across the resting nerve membrane Leakage of Potassium and Sodium Through the Nerve Membrane. The right side of Figure below shows a channel protein in the nerve membrane through which potassium and sodium ions can leak, called a potassium-sodium (K+ -Na+) “leak” channel. The emphasis is on potassium leakage because, on average, the channels are far more permeable to potassium than to sodium, normally about 100 times as permeable. As discussed later, this differential in permeability is exceedingly important in determining the level of the normal resting membrane potential.
Origin of the Normal Resting Membrane Potential
The figure shows the important factors in the establishment of the normal resting membrane potential of–90 millivolts. They are as follows.
1. Contribution of the Potassium Diffusion Potential.
In the figure below1A, we make the assumption that the only movement of ions through the membrane is diffusion of potassium ions, as demonstrated by the open channels between the potassium symbols (K+) inside and outside the membrane. Because of the high ratio of potassium ions inside to outside, 35:1, the Nernst potential corresponding to this ratio is –94 millivolts because the logarithm of 35 is 1.54, and these times –61millivolts is –94 millivolts. Therefore, if potassium ions were the only factor causing the resting potential, the resting potential inside the ﬁber would be equal to –94 millivolts, as shown in the ﬁgure.
2. Contribution of Sodium Diffusion through the Nerve Membrane.
The figure shows the addition of slight permeability of the nerve membrane to sodium ions, caused by the minute diffusion of sodium ions through the K+ -Na leak channels. The ratio of sodium ions from inside to outside the membrane is 0.1, and this gives a calculated Nernst potential for the inside of the membrane of +61 millivolts. But also shown in Figure 1B is the Nernst potential for potassium diffusion of –94 millivolts. How do these interact with each other, and what will be the summated potential? This can be answered by using the Goldman equation described previously. Intuitively, one can see that if the membrane is highly permeable to potassium but only slightly permeable to sodium, it is logical that the diffusion of potassium con tributes far more to the membrane potential than does the diffusion of sodium. In the normal nerve ﬁber, the permeability of the membrane to potassium is about 100 times as great as its permeability to sodium. Using this value in the Goldman equation gives a potential inside the membrane of –86 millivolts, which is near the potassium potential shown in the figure.
3. Contribution of the Na -K Pump.
In Figure 1C, the Na+ -K+ pump is shown to provide an additional contribution to the resting potential. In this ﬁgure, there is continuous pumping of three sodium ions to the outside for each two potassium ions pumped to the inside of the membrane. The fact that more sodium ions are being pumped to the outside than potassium to the inside causes continual loss of positive charges from inside the membrane; this creates an additional degree of negativity (about –4 millivolts additional) on the inside beyond that which can be accounted for by diffusion alone. Therefore, as shown in Figure 1C, the net membrane potential with all these factors operative at the same time is about –90 millivolts.
In summary, the diffusion potentials alone caused by potassium and sodium diffusion would give a membrane potential of about –86 millivolts, almost all of this being determined by potassium diffusion. Then, an additional –4 millivolts is contributed to the membrane potential by the continuously acting electrogenic Na+ -K+ pump, giving a net membrane potential of –90 millivolts.