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Title: Window Ca2+ current and its modulation by Ca2+ release in cardiac myocytes from dogs with chronic atrioventricular block
Authors: Antoons, Gudrun
Volders, Paul Ga
Stankovicova, Tania
Bito, Virginie
Stengl, Milan
Vos, Marc A
Sipido, Karin # ×
Issue Date: Feb-2007
Publisher: Cambridge University Press
Series Title: Journal of Physiology-London vol:579 issue:1 pages:147-160
Abstract: Torsade-de-Pointes (TdP) ventricular tachycardia typically occurs in the setting of early afterdepolarizations; it contributes to arrhythmias and sudden death in congenital and acquired heart disease. Window L-type Ca2+ current (ICaL) has a central role in the arrhythmogenesis and may be particularly important under beta-adrenergic stimulation. We studied the properties of ICaL in myocytes from the dog with chronic atrioventricular block (cAVB), which has cardiac hypertrophy and an increased susceptibility to TdP. Peak ICaL densities at baseline (K+- and Na+-free solutions, 10 mmol/L [EGTA]pip) in cAVB were comparable to control, but inactivation was shifted to the right resulting in a larger window current area in cAVB. Under beta-adrenergic stimulation, the window current area was increased and shifted to the left but less so in cAVB (maximum at -27 mV vs. -32 mV in control). ICaL during a step to -35 mV showed a transient reduction immediately after the peak. Test steps to 0 mV, simultaneous recording of [Ca2+]i and manipulation of sarcoplasmic reticulum (SR) Ca2+ release showed that this resulted from inhibition and fast recovery of ICaL with SR Ca2+ release. The extent of this dynamic modulation was larger in cAVB than in control (23+/-2% of the initially available current vs. 13+/-3%, P<0.05). EADs in cAVB myocytes under beta-adrenergic stimulation typically occurred in the window current voltage range and after decline of [Ca2+]i. In conclusion, in cAVB the larger window current, its rightward shift and enhanced dynamic modulation by SR Ca2+ release may contribute to an increased incidence of EADs in cAVB under beta-adrenergic stimulation.
URI: 
ISSN: 0022-3751
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiology
Cardiology
× corresponding author
# (joint) last author

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