Figure 22-9b illustrates how the membrane potential will change if enough Na⁺ channels in the plasma membrane open. The resulting influx of positively charged Na⁺ ions into the cytosol will more than compensate for the efflux of K⁺ ions through open resting K⁺ channels. The result will be a net inward movement of cations, generating an excess of positive charges on the cytosolic face of the plasma membrane and a corresponding excess of negative charges on the extracellular face (owing to the Cl⁻ ions “left behind” in the extracellular medium after influx of Na⁺ ions). In other words, the plasma membrane becomes depolarized to such an extent that the inside face becomes positive with respect to the external face.

Recall from Chapter 11 that the equilibrium potential of an ion is the membrane potential at which there is no net flow of that ion from one side of the membrane to the other due to the balancing of two opposing forces, the ion concentration gradient and the membrane potential. At the peak of depolarization in an action potential, the magnitude of the membrane potential is very close to the Na⁺ equilibrium potential E_Na given by the Nernst equation (Equation 11-2), as would be expected if opening of voltage-gated Na⁺ channels is responsible for generating action potentials. For example, the measured peak value of the action potential for the squid giant axon is +35 mV, which is close to the calculated value of E_Na (+55 mV) based on Na⁺ concentrations of 440 mM outside and 50 mM inside. The relationship between the magnitude of the action potential and the concentration of Na⁺ ions inside and outside the cell has been confirmed experimentally. For instance, if the concentration of Na⁺ ions in the solution bathing the squid axon is reduced to one-third of normal, the magnitude of the depolarization is reduced by 40 mV, nearly as predicted.

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