Activation of background membrane conductance by the tyrosine kinase inhibitor tyrphostin A23 and its inactive analog tyrphostin A1 in guinea pig ventricular myocytes

The effects of the tyrosine kinase (TK) inhibitor tyrphostin A23 and its in active analog tyrphostin At on background membrane conductance were investi gated in guinea pig ventricular myocytes. TK-inhibiting A23 reversibly incr eased membrane conductance under conditions designed to minimize Na, Ca2+, K+, and Na+-K+ pump currents. Similar stimulatory action was obtained with TK-inactive At. The tyrphostin-induced current was inhibited by omitting ex ternal Na+ or Ca2+, suppressed by chelating internal Ca2+, blocked by exter nal Cd2+ and Ni2+, and insensitive to changes in internal Cl- concentration . We conclude that tyrphostins have a direct, TK-independent action that in creases membrane conductance probably by stimulating Na+-Ca2+ exchange.