Comparison of the effects of internal TEA+ and Cs+ on potassium current in squid giant axons

Internal tetraethylammonium (TEA) and cesium ions block outward potassium current in nerve membrane in a voltage-dependent manner. Blockade with Cs+ occurs virtually instantaneously after membrane depolarization, whereas blockade with TEA+ occurs after a delay. The latter result suggested to Armstrong (1966, J. Gen. Physiol., 50:279-293; 1969, J. Gen. Physiol., 54:553-575) that potassium channels must open before TEA+ blockade can occur, which is in contrast to Cs+ blockade, which appears to be independent of channel gating. The results in this study concerning the effect of TEA+ on inward (tail) current argue against the Armstrong model. Specifically, TEA+ (partially) blocks inward current without altering the tail current time constant. This result indicates that TEA+ can occupy its binding site within the channel whether or not the channel gates are open. This alternative hypothesis can describe both the steady-state and time-dependent components of TEA+ blockade.