Abstract

THE inward sodium current underlying the nerve action potential is carried by discrete Na channels1 in the membrane which are gated in response to the membrane potential. A basic question in understanding the gating mechanism is whether the conductance of the channels has only two states, open and closed, or whether there are more states, with the channel conductance progressing from one level to another to give the variable membrane conductance observed in voltage-clamp experiments. The ensemble fluctuation measurements reported here are consistent with the simple interpretation that Na channels have only two principal conductance states, with conductances of 0 and 7.7 ± 1 pS (near zero membrane potential), and number approximately 5 × 104 in the node of Ranvier of a 14 µm diameter frog myelinated nerve fibre. Like stationary fluctuation analysis2, the experimental method described here can yield information about the size and kinetics of the single gating events in ionic channels, but is also applicable to non-stationary processes such as membrane conductances that activate or inactivate with time. I report here measurements of the mean Na current and the variance at various times after the start of a depolarising pulse, using an ensemble of successively evoked current transients.

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