K-current fluctuations in inward-rectifying channels of frog skeletal muscle.

K currents and K-current fluctuations were recorded in inwardly rectifying K channels of frog skeletal muscle under voltage-clamp conditions. External application of 0.2 to 10 mM Cs reduces the inward mean K current but produces a distinct increase of the spectral density of K-current fluctuations. The additional fluctuations arise from the random blocking by Cs ions. From the variance of current fluctuations, the steady-state current and the probability of the open unblocked channel an effective single-channel conductance gamma* was calculated. Gamma* strongly depends on the external Cs concentration (7.8 pS at 0.2 mM Cs, 2.1 pS at 10 mM Cs). This dependence is interpreted in terms of a two-step blocking process: (1) a fast exchange of Cs ions between the external solution and a first binding site inside the channel which leads to the Cs-modulated effective single-channel conductance, and (2) a slow Cs binding to a second site deeper in the channel which produces the observed current fluctuations. With this hypothesis we obtained a real single-channel conductance of gamma approximately equal to 10 pS and a real density of n approximately equal to 4 inwardly rectifying channels per micrometer2 of muscle surface area.