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 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.
Ogura
T
T
Second Department of Physiology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan. physiol2@kanazawa-med.ac.jp
Imanishi
S
S
Shibamoto
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D020032:Tyrphostins; D012964:Sodium; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23; D002118:Calcium