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 (I(Na)) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of I(Na) inactivation and 1 microM staurosporine reduced amplitude of I(Na) about 33%. Staurosporine decreased I(Na) at all potentials and slowed the I(Na) inactivation in a dose-dependent manner, with a Kd value of 1.107+/-0.162 microM. 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 microM) and chelerythrine (3 microM), did not show a slowing effect on I(Na) inactivation. In conclusion, our results indicate that the slowing of I(Na) 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.
Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Jae Hong
JH
Ko
Won Sun
WS
Park
Sung Joon
SJ
Kim
Yung E
YE
Earm
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D015222:Sodium Channels; D012964:Sodium; D011493:Protein Kinase C; D019311:Staurosporine