Tuning L-Type Ca2+ Current Properties to Suppress Early After depolarizations

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Targeting the late component of the cardiac L-type Ca2+ current to suppress early afterdepolarizations

Early afterdepolarizations (EADs) associated with prolongation of the cardiac action potential (AP) can create heterogeneity of repolarization and premature extrasystoles, triggering focal and reentrant arrhythmias. Because the L-type Ca(2+) current (ICa,L) plays a key role in both AP prolongation and EAD formation, L-type Ca(2+) channels (LTCCs) represent a promising therapeutic target to norm...

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Certain signaling events that promote L-type Ca2+ channel (LCC) phosphorylation, such as beta-adrenergic stimulation or an increased expression of Ca(2+)/calmodulin-dependent protein kinase II, promote mode 2 gating of LCCs. Experimental data suggest the hypothesis that these events increase the likelihood of early after-depolarizations (EADs). We test this hypothesis using an ionic model of th...

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Targeting the late component of the cardiac L-type Ca current to suppress early afterdepolarizations

Early afterdepolarizations (EADs) are arrhythmogenic membrane potential oscillations that occur before repolarization of the cardiac action potential (AP) is complete. Although the mechanistic link between EADs in single cells and triggered arrhythmias in the heart is still a subject of intense investigation (Wit and Rosen, 1983; Rosen, 1988; Antzelevitch and Sicouri, 1994; El-Sherif et al., 19...

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Rational strategy to stop arrhythmias: Early afterdepolarizations and L-type Ca2+ current

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ژورنال

عنوان ژورنال: Biophysical Journal

سال: 2013

ISSN: 0006-3495

DOI: 10.1016/j.bpj.2012.11.1646