Inhibition of L-type calcium current by genistein, a tyrosine kinase inhibitor, in pregnant rat myometrial cells

Biochim Biophys Acta. 1995 Dec 13;1240(2):196-200. doi: 10.1016/0005-2736(95)00191-3.


Possible regulation of L-type Ca2+ channels by tyrosine kinase was examined in freshly isolated uterine smooth muscle cells obtained from late pregnant (18-19 day) rat, using whole-cell voltage clamp. Bath application of genistein, an inhibitor of tyrosine kinase, decreased L-type Ca2+ current (ICa(L)) dose-dependently. The maximal inhibition of ICa(L) was 46% and the concentration for half-maximal inhibition (IC50) was 50 microM (at a holding potential of -60 mV). The effect of genistein was reversible. Daidzein, an inactive analog of genistein, had no inhibitory effect on ICa(L) at concentrations as high as 300 microM. The steady-state inactivation curve for ICa(L) was shifted to the left by genistein (15 mV at 100 microM), whereas the activation curve was not affected, suggesting that genistein exerts.a voltage-dependent block. These results suggest that the L-type Ca2+ channels in myometrial cells may be modulated by endogenous tyrosine kinase, i.e., they are in a tonically stimulated state due to tyrosine kinase activity. This modulatory mechanism may play a role on the regulation of Ca2+ influx and uterine contraction during normal labor and preterm labor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Female
  • Genistein
  • Isoflavones / pharmacology*
  • Muscle, Smooth / drug effects
  • Myometrium / drug effects
  • Myometrium / metabolism*
  • Patch-Clamp Techniques
  • Pregnancy
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley


  • Calcium Channels
  • Isoflavones
  • Genistein
  • Protein-Tyrosine Kinases