Effect of genistein on L-type calcium channel currents of proximal colon smooth muscle cells of guinea-pig / 中国药理学与毒理学杂志

ABSTRACT

AIM To study the effect of genistein (GST), a protein tyrosine kinases inhibitor, on L-type calcium channel currents (Iba,L or Ica,L, dependent on permeating ion used) in freshly dispersed colon smooth muscle cells from guinea-pig. METHODS Single colon smooth muscle cells were enzymatically dissociated from guinea-pig. L-type calcium currents were measured by conventional whole-cell patch-clamp techniques. RESULTS The peak amplitudes of Iba,L elicited to 10 mV test potential from a holding potential of -80 mV, were reversibly and dose-dependently reduced by GST (10-100 μmol·L-1) with an IC50 value of (39.9±3.6)μmol·L-1. Bath application of GST shifted the steady-state inactivation curves of Iba,L in a hyperpolarized direction (about 10 mV, P＜0.01) without altering their slopes. The peak amplitudes of Iba,L were also inhibited but to a less extent by daidzein, an inactive analogue of GST. Sodium orthovanadate 1 mmol·L-1, a potent inhibitor of protein tyrosine phosphatases, blocked GST-induced inhibition of Ica,L. CONCLUSION GST can block L-type calcium channel activity in guinea-pig colon smooth muscle cells via tyrosine kinase pathway.