Influence of Channel Subunit Composition on L-type Ca2+ Current Kinetics and Cardiac Wave Stability.
From: Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles 90095-7115, USA.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Sep 2007
- ISSN: 0363-6135
- Volume: 293
- Issue: 3
- Pages: H1805-15
- Medium: Print
- Language: English
- Citation (JAMA): Gudzenko Vadim, Shiferaw Yohannes, Savalli Nicoletta, et al. Influence of Channel Subunit Composition on L-type Ca2+ Current Kinetics and Cardiac Wave Stability.. Am. J. Physiol. Heart Circ. Physiol. Sep 2007;293:H1805-15
Abstract
Previous studies have demonstrated that the slope of the function relating the action potential duration (APD) and the diastolic interval, known as the APD restitution curve, plays an important role in the initiation and maintenance of ventricular fibrillation. Since the APD restitution slope critically depends on the kinetics of the L-type Ca(2+) current, we hypothesized that manipulation of the subunit composition of these channels may represent a powerful strategy to control cardiac arrhythmias. We studied the kinetic properties of the human L-type Ca(2+) channel (Ca(v)1.2) coexpressed with the alpha(2)delta-subunit alone (alpha(1C) + alpha(2)delta) or in combination with beta(2a), beta(2b), or beta(3) subunits (alpha(1C) + alpha(2)delta + beta), using Ca(2+) as the charge carrier. We then incorporated the kinetic properties observed experimentally into the L-type Ca(2+) current mathematical model of the cardiac action potential to demonstrate that the APD restitution slope can be selectively controlled by altering the subunit composition of the Ca(2+) channel. Assuming that beta(2b) most closely resembles the native cardiac L-type Ca(2+) current, the absence of beta, as well as the coexpression of beta(2a), was found to flatten restitution slope and stabilize spiral waves. These results imply that subunit modification of L-type Ca(2+) channels can potentially be used as an antifibrillatory strategy.
Mesh Headings (Keywords): Action Potentials, Animals, Arrhythmias, Cardiac, Calcium Channels, L-Type, Electrophysiology, Female, Heart Conduction System, Humans, Models, Biological, Patch-Clamp Techniques, Protein Subunits, Transfection, Ventricular Fibrillation, Xenopus laevis
Check for Full Text / PubMed Unique Identifier (PMID): 17545475
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.