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

Cited 9 time in Web of Science Cited 9 time in Scopus
Authors
Ko, Jae Hong; Park, Won Sun; Kim, Sung Joon; Earm, Yung E.
Issue Date
2006-02-21
Publisher
Elsevier
Citation
Eur J Pharmacol. 2006 Mar 18;534(1-3):48-54. Epub 2006 Feb 20.
Keywords
AnimalsDose-Response Relationship, DrugHeart Atria/cytology/drug effects/metabolism*Ion Channel GatingKineticsMembrane PotentialsMyocytes, Cardiac/cytology/drug effects/metabolismProtein Kinase C/antagonists & inhibitorsProtein Kinase Inhibitors/*pharmacologyRabbitsSodium/metabolismSodium Channels/*drug effects/metabolismStaurosporine/*pharmacology
Abstract
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.
ISSN
0014-2999 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16488408

http://hdl.handle.net/10371/27719
DOI
https://doi.org/10.1016/j.ejphar.2006.01.018
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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