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Am J Physiol Heart Circ Physiol 276: H1724-H1733, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 5, H1724-H1733, May 1999

L-type Ca2+ current in guinea pig ventricular myocytes treated with modulators of tyrosine phosphorylation

Toshitsugu Ogura, Lesya M. Shuba, and Terence F. McDonald

Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Guinea pig ventricular myocytes in whole cell configuration were treated with tyrosine kinase (TK) inhibitors [genistein (Gst), tyrphostin A23 (T23), and tyrphostin A25 (T25)] and with inactive analogs [daidzein, genistin, and tyrphostin A1 (T1)] to measure effects on L-type Ca2+ current (ICa,L). Gst inhibited ICa,L (IC50 = 47 µM) without affecting its time course or shifting the ICa,L-voltage relationship. At the highest concentration of isoflavone tested (200 µM), ICa,L was inhibited by 66 ± 7% (Gst), 22 ± 2% (daidzein), and 1 ± 3% (genistin). Inhibition of ICa,L by the active tyrphostins was significantly larger than inhibition by T1; at 200 µM the inhibitions were 72 ± 6% (T23), 71 ± 6% (T25), and 27 ± 6% (T1). The phosphotyrosine phosphatase inhibitor orthovanadate (1 mM) had a small stimulatory effect (6 ± 2%) on basal ICa,L and blocked the inhibition of ICa,L by TK inhibitors. The data suggest a role for the TK-phosphotyrosine phosphatase system in the regulation of cardiac Ca2+ channels.

genistein; daidzein; tyrphostins; orthovanadate; protein tyrosine kinase


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