S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Physiology (생리학교실) Journal Papers (저널논문_생리학교실)
Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes
- Ko, Jae Hong; Park, Won Sun; Kim, Sung Joon; Earm, Yung E.
- Issue Date
- Eur J Pharmacol. 2006 Mar 18;534(1-3):48-54. Epub 2006 Feb 20.
- Animals; Dose-Response Relationship, Drug; Heart Atria/cytology/drug effects/metabolism; *Ion Channel Gating; Kinetics; Membrane Potentials; Myocytes, Cardiac/cytology/drug effects/metabolism; Protein Kinase C/antagonists & inhibitors; Protein Kinase Inhibitors/*pharmacology; Rabbits; Sodium/metabolism; Sodium Channels/*drug effects/metabolism; Staurosporine/*pharmacology
- 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.
- 0014-2999 (Print)
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