A computational investigation of cardiac caveolae as a source of persistent sodium current.

A computational investigation of cardiac caveolae as a source of persistent sodium current.
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DOI:
10.3389/fphys.2011.00087
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发表时间:
2011
影响因子:
4
通讯作者:
Shibata EF
Shibata EF
中科院分区:
医学2区
文献类型:
--
作者:
Besse IM;Mitchell CC;Hund TJ;Shibata EF

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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.
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