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

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

Unlike the brief action potentials (APs) in skeletal myo­ cytes or neurons, the human cardiac AP takes 100s of milliseconds to repolarize the cell. This slow repolar­ ization is essential for proper excitation–contraction coupling in cardiac muscle, and precise control of AP duration contributes to electrical stability. Under vari­ ous pathological conditions, often when the AP dura­ tion is pr...

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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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Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current.

Early afterdepolarizations (EADs) are a type of triggered activity found in heart muscle. We used voltage-clamped sheep cardiac Purkinje fibers to examine the mechanism underlying EADs induced near action potential plateau voltages with the Ca2+ current agonist Bay K 8644 and the effect of several interventions known to suppress or enhance these EADs. Bay K 8644 produced an inward shift of the ...

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Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias.

Clinical studies have shown that sudden death is initiated by an illtimed propagated ectopic beat that leads to fibrillation. –4 However, the mechanism underlying these focal excitations is not completely understood. Experimental studies have demonstrated that abnormal calcium (Ca2+) cycling is a critical factor in the development of focal excitations. 9 These excitations can be caused by spont...

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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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ژورنال

عنوان ژورنال: Journal of General Physiology

سال: 2015

ISSN: 1540-7748,0022-1295

DOI: 10.1085/jgp.201511429