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Blocking of the squid axon potassium channel by external caesium ions.

1. The blocking by external Cs of inward tail currents though the K channel of the squid giant axon, as seen by the effect of Cs on the 'instantaneous' I‐V curve is described. 2. Block onset is complete within 50‐‐100 musec of a step in voltage. The block produces a negative slope region in the inward current quadrants of the I‐V plots. 3. The experiments were performed in the presence of external concentrations of 240 mM‐K and 0‐200 mM‐Cs, with the external ionic strength maintained by substituting Tris or Na for the Cs. Essentially the same results were obtained with either Tris or Na as the substitute ion. 4. The concentration of Cs required to block 50% of the K channels at zero transmembrane voltage, in intact axons, was estimated to be approximately 1 M. 5. The slope of the dose‐response curve is steeper than expected for a blocking reaction with 1:1 stoichiometry when membrane voltage is in the neighbourhood of 100 mV. 6. With Cs concentrations greater than or approximately 50 mM, the voltage dependence of the block is too steep to be accounted for by the binding of a single Cs ion per channel within the membrane electric field. 7. In perfused axons, the block occurred at less negative internal voltage when internal K concentration was reduced. 8. These observations are qualitatively consistent with a multisite channel showing single file properties.