Jpn. J. Pharmacol. 87 (3), 235-239 (2001)

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

Toshitsugu Ogura*, Sunao Imanishi and Toshishige Shibamoto

Second Department of Physiology, Kanazawa Medical University, 1-1, Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan

*Corresponding author. FAX: +81-76-286-8010, E-mail:

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+-Ca2+ exchange.

Keywords: Tyrphostin, Tyrosine kinase, Na+-Ca2+ exchange

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