Genistein inhibition of fast Na + current in uterine leiomyosarcoma cells is independent of tyrosine kinase inhibition

Abstract

Possible regulation of fast Na + channels by tyrosine kinase was examined in a human uterine smooth muscle cell line, using whole-cell voltage clamp (at a holding potential of −90 mV). Bath application of genistein, an inhibitor of tyrosine kinase, decreased the fast Na + current ( I Na( f) ) dose-dependently. The maximal inhibition of I Na(f) was 98%, and the concentration for half-maxima inhibition (IC 50) was 9 μM. The effect of genistein was rapidly reversible. Daidzein, an inactive analog of genistein, had a similar inhibitory effect on I Na(f). These results suggest that the fast Na + channels in uterine sarcoma cells may be directly blocked by genistein and daidzein, i.e., their effect may be independent of tyrosine kinase inhibition.