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A Computational Investigation of Cardiac Caveolae as a Source of Persistent Sodium Current
Journal article   Open access   Peer reviewed

A Computational Investigation of Cardiac Caveolae as a Source of Persistent Sodium Current

Ian M Besse, Colleen C Mitchell, Thomas J Hund and Erwin F Shibata
Frontiers in physiology, Vol.2, pp.87-87
11/30/2011
DOI: 10.3389/fphys.2011.00087
PMCID: PMC3229093
PMID: 22144962
url
https://doi.org/10.3389/fphys.2011.00087View
Published (Version of record) Open Access

Abstract

Recent studies of cholesterol-rich membrane microdomains, called caveolae, reveal that caveolae are reservoirs of “recruitable” sodium ion channels. Caveolar channels constitute a substantial and previously unrecognized source of sodium current in cardiac cells. In this paper we model for the first time caveolar sodium currents and their contributions to cardiac action potential morphology. We show that the β -agonist-induced opening of caveolae may have substantial impacts on peak overshoot, maximum upstroke velocity, and ultimately conduction velocity. Additionally, we show that prolonged action potentials and the formation of potentially arrhythmogenic afterdepolarizations, can arise if caveolae open intermittently throughout the action potential. Our simulations suggest that caveolar sodium current may constitute a route, which is independent of channelopathies, to delayed repolarization and the arrhythmias associated with such delays.
cardiomyocyte caveolae caveolin-3 LQT9 mathematical model Physiology β-adrenergic

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