Activation of Background Membrane Conductance by the Tyrosine Kinase Inhibitor Tyrphostin A23 and Its Inactive Analog Tyrphostin A1 in Guinea Pig Ventricular Myocytes

Abstract

The effects of the tyrosine kinase (TK) inhibitor tyrphostin A23 and its inactive analog tyrphostin A1 on background membrane conductance were investigated in guinea pig ventricular myocytes. TK-inhibiting A23 reversibly increased membrane conductance under conditions designed to minimize Na⁺, Ca²⁺, K⁺, and Na⁺-K⁺ pump currents. Similar stimulatory action was obtained with TK-inactive A1. The tyrphostin-induced current was inhibited by omitting external Na⁺ or Ca²⁺, suppressed by chelating internal Ca²⁺, blocked by external Cd²⁺ and Ni²⁺, and insensitive to changes in internal Cl⁻ concentration. We conclude that tyrphostins have a direct, TK-independent action that increases membrane conductance probably by stimulating Na⁺-Ca ²⁺ exchange.