Influence of channel subunit composition on L-type Ca^sup 2+^ current kinetics and cardiac wave stability

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 critic...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2007-09, Vol.293 (3), p.H1805
Main Authors: Gudzenko, Vadim, Shiferaw, Yohannes, Savalli, Nicoletta, Vyas, Roshni
Format: Article
Language:English
Subjects:
Calcium
Cardiac arrhythmia
Cells
Gene expression
Kinetics
Mathematical models
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Summary: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... 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... channel (Ca...1.2) coexpressed with the α...-subunit alone (α... + α...) or in combination with β..., β..., or β... subunits (α... + α... + β), using Ca... as the charge carrier. We then incorporated the kinetic properties observed experimentally into the L-type Ca... 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... channel. Assuming that β... most closely resembles the native cardiac L-type Ca... current, the absence of β, as well as the coexpression of β..., was found to flatten restitution slope and stabilize spiral waves. These results imply that subunit modification of L-type Ca... channels can potentially be used as an antifibrillatory strategy. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0363-6135
1522-1539