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PMID: 9482712 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effect of bay K 8644 (-) and the beta2a subunit on Ca2+-dependent inactivation in alpha1C Ca2+ channels.

The Journal of general physiology ·Vol. 111 ·No. 3 ·1998-03-00 ·Pages 463-75

Noceti F, Olcese R, Qin N, Zhou J, Stefani E

Abstract

Ca2+ currents recorded from Xenopus oocytes expressing only the alpha1C pore-forming subunit of the cardiac Ca2+ channel show Ca2+-dependent inactivation with a single exponential decay. This current-dependent inactivation is not detected for inward Ba2+ currents in external Ba2+. Facilitation of pore opening speeds up the Ca2+-dependent inactivation process and makes evident an initial fast rate of decay. Facilitation can be achieved by (a) coexpression of the beta2a subunit with the alpha1C subunit, or (b) addition of saturating Bay K 8644 (-) concentration to alpha1C channels. The addition of Bay K 8644 (-) to alpha1Cbeta2a channels makes both rates of inactivation faster. All these maneuvers do not induce inactivation in Ba2+ currents in our expression system. These results support the hypothesis of a mechanism for the Ca2+-dependent inactivation process that is sensitive to both Ca2+ flux (single channel amplitude) and open probability. We conclude that the Ca2+ site for inactivation is in the alpha1C pore-forming subunit and we propose a kinetic model to account for the main features of alpha1Cbeta2a Ca2+ currents.

MeSH Terms
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology Animals Calcium Channel Agonists/pharmacology Calcium Channels/drug effects,physiology DNA, Complementary Electric Stimulation Electrophysiology Heart/physiology In Vitro Techniques Kinetics Models, Molecular Oocytes Xenopus laevis
Chemicals
Calcium Channel Agonists Calcium Channels DNA, Complementary 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Noceti F
Department of Anesthesiology, School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1778, USA.
Olcese R
Qin N
Zhou J
Stefani E
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Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
0022-1295
DOI
10.1085/jgp.111.3.463
Published
1998-03-00
Pages
463-75
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC2217112
Subset
IM
Grants
NIAMS NIH HHS · AR-38970 · United States
NIGMS NIH HHS · GM17120-02 · United States
External Links
PubMed source DOI: 10.1085/jgp.111.3.463 PMC Full Text View journal details
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