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This Article Full Text Full Text (PDF) All Versions of this Article: 579/1/147    most recent jphysiol.2006.124222v2 jphysiol.2006.124222v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Antoons, G. Articles by Sipido, K. R. Search for Related Content PubMed PubMed Citation Articles by Antoons, G. Articles by Sipido, K. R. Related Collections Cardiovascular

¹ Laboratory of Experimental Cardiology, University of Leuven, Belgium
² Department of Cardiology, Academic Hospital Maastricht, The Netherlands
³ Department of Medical Physiology, University Medical Center, Utrecht, The Netherlands
⁴ Department of Pharmacology and Toxicology, Comenius University, Bratislava, Slovakia
⁵ Department of Physiology, Charles University, Medical School Plzen, Czech Republic

Torsades 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 (I_CaL) has a central role in the arrhythmogenesis and may be particularly important under -adrenergic stimulation. We studied the properties of I_CaL in myocytes from the dog with chronic atrioventricular block (cAVB) that has cardiac hypertrophy and an increased susceptibility to TdP. Peak I_CaL densities at baseline (K⁺- and Na⁺-free solutions, 10 mmol l^–1 [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 -adrenergic stimulation, the window current area was increased and shifted to the left, but less so in cAVB (maximum at –27 mV, versus –32 mV in control). I_CaL 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 I_CaL with SR Ca²⁺ release. The extent of this dynamic modulation was larger in cAVB than in control (23 ± 2% of the initially available current, versus 13 ± 3%; P < 0.05). Early afterdepolarizations (EADs) in cAVB myocytes under -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 -adrenergic stimulation.

(Received 3 November 2006; accepted after revision 24 November 2006; first published online 30 November 2006)
Corresponding author K. R. Sipido: Laboratory of Experimental Cardiology, KUL, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium. Email: Karin.Sipido{at}med.kuleuven.ac.be

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				V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]