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

  • Jpn J Pharmacol. 2001 Nov;87(3):235-9. doi: 10.1254/jjp.87.235.
T Ogura  1 ,  S Imanishi ,  T Shibamoto
Affiliations
  • 1. Second Department of Physiology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan. [email protected]
PMID: 11885974 DOI: 10.1254/jjp.87.235
Abstract

ABSTRACT-The effects of the tyrosine kinase (TK) inhibitor tyrphostin A23 and its inactive analog tyrphostin Al 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 Al. The tyrphostin-induced current was inhibited by omitting external Na+ or Ca+, 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.

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