Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes

In this study, the effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on Na+ current (INa) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of INa inactivation and 1 μM staurosporine reduced amplitude of INa about 33%. Staurosporine decreased INa at all potentials and slowed the INa inactivation in a dose-dependent manner, with a Kd value of 1.107 ± 0.162 μM. Staurosporine did not change the recovery kinetics and show use dependence. However, the activation and the steady-state inactivation curves were shifted toward more negative potentials (− 5.5 and − 5.1 mV, respectively). Two other PKC inhibitors, GF 109203X (1 μM) and chelerythrine (3 μM), did not show a slowing effect on INa inactivation. In conclusion, our results indicate that the slowing of INa inactivation by staurosporine seems not to be through blockade of PKC rather to act directly on the Na+ channels, and the direct blocking effects of staurosporine on the Na+ channel should be taken into consideration when staurosporine is used in functional studies of ion channel modulation by protein phosphorylation.