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 (IN,f)) dose-dependently. The maximal inhibition of INane) was 98%, and the concentration for half-maximal inhibition (ICs0) was 9/xM. The effect of genistein was rapidly reversible. Daidzein, an inactive analog of genistein, had a similar inhibitor effect on INalf)' 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.
