Xv. Neurophysiology*

Resting squid nerve membrane actively extrudes Na+ against a large concentration gradient, while another cation, K + , is concentrated passively within the cell by the Donnan equilibrium. During the passage of an impulse, large transient current flows across the membrane; some K + leaves, some Na + enters, but which ions carry the current at which instant, and how it is turned on and off cannot be told from simple external measurements. Thus Marmont, and later, exhaustively, Hodgkin and Huxley, applied a voltage clamp between the inside and outside of a squid giant axon, i. e., they applied step functions of voltage across the membrane and measured the current required to maintain the steps. By systematically varying the external concentration of different ions they were finally brought to a description of the nonlinear behavior of the membrane in terms of specific ion conductances, each conductance being dependent on the concentration potential of its species and certain rate constants. With this very careful job they accurately predicted the shape of traveling nerve spikes and afterpotentials. However, that tour de force was meant to apply only to squid axon the subject of their experiments. Very soon other physiologists began using as laws interpretations which Hodgkin and Huxley had only diffidently suggested, and these laws were applied to nerve-nerve and nerve-muscle transmission with great ingenuity. While such guessing is fair in the absence of data, it is clear that one must in the event test, say, frog nerve, for what nonlinear conductances govern its behavior. Too many differences in chemical composition, speed of transmission, shape of spike, and so forth, exist between squid and frog nerve to allow the voltage-current relations for one to be used on the other. Some workers even suspect that certain quaternary amines rather than Na + are important in frog-nerve conduction. The physical difficulty of examining other than giant fibers is very great. One can insert down a squid nerve of some 0. 5 mm in diameter two reasonably large wires, one to measure voltage against some external probe, the other to supply current to some outer electrode. This technique is not possible with fibers that are only 10 . in diameter. Cell bodies some 50 1 across could, in principle, admit two microelectrodes, one acting as a point source of current, but such a measure would be valid only if the cell were spherical. (Eccles' results with bipolar microelectrodes are not relevant