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- Madhvani, Roshni V., et al.
(författare)
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Shaping a New Ca2+ Conductance to Suppress Early Afterdepolarizations in Cardiac Myocytes
- 2011
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Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 589:24, s. 6081-6092
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Tidskriftsartikel (refereegranskat)abstract
- Non‐technical summary Diseases, genetic defects, or ionic imbalances can alter the normal electrical activity of cardiac myocytes causing an anomalous heart rhythm, which can degenerate to ventricular fibrillation (VF) and sudden cardiac death. Well‐recognized triggers for VF are aberrations of the cardiac action potential, known as early afterdepolarizations (EADs). In this study, combining mathematical modelling and experimental electrophysiology in real‐time (dynamic clamp), we investigated the dependence of EADs on the biophysical properties of the L‐type Ca2+ current (ICa,L) and identified modifications of ICa,L properties which effectively suppress EAD. We found that minimal changes in the voltage dependence of activation or inactivation of ICa,L can dramatically reduce the occurrence of EADs in cardiac myocytes exposed to different EAD‐inducing conditions. This work assigns a critical role to the L‐type Ca2+ channel biophysical properties for EADs formation and identifies the L‐type Ca2+ channel as a promising therapeutic target to suppress EADs and their arrhythmogenic effects.
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