FAST SINGLE-CHANNEL MEASUREMENTS RESOLVE THE BLOCKING EFFECT OF CS+ ON THE K+ CHANNEL

The Cs+ block of K+ channels has often been investigated by methods that allow only indirect estimation of the rate constants of blocking and re-opening. This paper presents single-channel records with high temporal resolution which make the direct observation of the fast transitions between the blocked and the unblocked state possible. The rate constants k(CGb), k(GbO) of Cs+-dependent blocking and of re-opening are evaluated from the time constants found in the open-time and closed-time histograms. The blocking rate constant k(CGb) between 1000 and 50000 s(-1) depends linearly on the Cs+ concentration and strongly on voltage, increasing by a factor of 1.44 per 10 mV hyperpolarization. The re-opening rate constant k(GbO) approximate to 30000 s(-1) is independent of Cs+ concentration and only slightly voltage-dependent. Formally, the results can be described by a Woodhull-model. The strong voltage dependence with d> 1, however, weakens its plausibility. The results are interpreted in terms of a molecular framework emerging from recent results on the structure of voltage-gated channels.