VOLTAGE-DEPENDENT INHIBITION OF THE NA+,K+ PUMP BY TETRAETHYLAMMONIUM

Tetraethylammonium (TEA(+)) is an effective inhibitor of a variety of K+-channels, and has been widely used to reduce K+-sensitive backgroun d conductances in electrophysiological investigations of the Na+,K+-AT Pase. Here we demonstrate by combination of two-electrode voltage clam p (TEVC) and giant patch clamp of Xenopus oocytes, and measurements of the activity of purified ATPase of pig kidney that TEA(+) directly in hibits the Na+,K+-ATPase from the outside. The K-I value in TEVC exper iments at 0 mV is about 10 mM increasing with more negative potentials . A similar voltage-dependent inhibition by TEA(+) was observed in the excised membrane patches except that the apparent K-I value at 0 mV i s about 100 mM, a value nearly identical to that found for inhibition of purified kidney ATPase. The voltage-dependent inhibition can be des cribed by an effective valency of 0.39 and is attributed to an interfe rence with the voltage-dependent binding of K+ at an external access c hannel. The apparent dielectric length of the access channel for K+ is not affected by TEA(+). (C) 1998 Elsevier Science B.V. All rights res erved.