K(+)‐independent Kir blockade by external Cs(+) and Ba(2+)

Cations such as Cs(+) and Ba(2+) are known to block K(+) currents by entering an open channel and binding to the selectivity filter, where they obstruct the pore and block diffusion of the permeant ion. This obstruction is voltage‐ and K(+)‐dependent and is relieved by the trans permeant ion flux. The present patch‐clamp study on Xenopus muscle cells shows that, unlike the voltage‐activated K(+) (Kv) channels, blockade of the inward rectifier K(+) (Kir) channels by external foreign cations results from the combination of pore obstruction with a new and independent mechanism. This new blockade is independent of the K(+) concentrations and flux and acts indiscriminately on both the outward and the inward Kir components. External Cs(+) and Ba(2+) compete for this blockade with free access to common channel sites. These features suggest that the blocking cations do not need to enter the channel for this new mechanism, and should bind to the extracellular side of the channel. When K(+) fluxes are flowing outward, the pore obstruction is relieved for both Kir and Kv currents, and the K(+)‐independent blockade here described is responsible for a selective Kir inhibition, justifying the use of these external cations as tools in cell physiology studies.