When current of proper polarity and sufficient intensity is passed across isolated frog skin or toad bladder, an action potential of about 200 mv and 10 msec. duration with a sharp threshold and refractory period of several seconds' duration is elicited. Interruption of current during the action potential abolishes the response, and, as shown by appropriate bridge measurements, this occurs because the action potential results from resistance variations during the current flow. The ionic composition of the medium bathing the frog skin was varied, and it was found that the response is relatively insensitive to changes in the solution bathing the inner surface, but rapidly and reversibly affected by changes in the outer solution, particularly by replacement of sodium with potassium and by variations of calcium concentration. It was also observed that the resistance of the skin and action potential across it are reversibly altered by metabolic inhibitors and that these alterations occur independently of any changes in the intrinsic EMF of the system. From the finding that the action potential across frog skin and toad bladder results from a time-variant resistance, it is argued that this same phenomenon can be the basis of electrical excitability in general. This would attribute physical significance to the equivalent circuit commonly employed to represent the plasma membrane; i.e., the plasma membrane would be a mosaic structure of spatially separate permselective regions.

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