Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle

The Journal of Clinical Investigation
E MarbanW G Wier

Abstract

Drug-induced triggered arrhythmias in heart muscle involve oscillations of membrane potential known as delayed or early afterdepolarizations (DADs or EADs). We examined the mechanism of DADs and EADs in ferret ventricular muscle. Membrane potential, tension and aequorin luminescence were measured during exposure to elevated [Ca2+]0, strophanthidin and/or isoproterenol (to induce DADs), or cesium chloride (to induce EADs). Ryanodine (10(-9)-10(-6) M), an inhibitor of Ca2+ release from the sarcoplasmic reticulum, rapidly suppressed DADs and triggered arrhythmias. When cytoplasmic Ca2+-buffering capacity was enhanced by loading cells with the Ca2+ chelators BAPTA or quin2, DADs were similarly inhibited, as were contractile force and aequorin luminescence. In contrast to DADs, EADs induced by Cs were not suppressed by ryanodine or by loading with intracellular Ca2+ chelators. The possibility that transsarcolemmal Ca2+ entry might produce EADs was evaluated with highly specific dihydropyridine Ca channel agonists and antagonists. Bay K8644 (100-300 nM) potentiated EADs, whereas nitrendipine (3-20 microM) abolished EADs. We conclude that DADs and DAD-related triggered arrhythmias are activated by an increase in intracellular free Ca2...Continue Reading

References

Sep 1, 1978·British Heart Journal·S Gavrilescu, C Luca
Mar 1, 1985·Circulation Research·M Valdeolmillos, D A Eisner
May 1, 1983·The Journal of General Physiology·B P BeanR W Tsien
Feb 1, 1984·Circulation Research·I R JosephsonA M Brown
Jan 1, 1984·British Journal of Pharmacology·M R MitchellV W Twist
Dec 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·W G WierE Marban
Jan 1, 1982·Progress in Biophysics and Molecular Biology·J R BlinksF G Prendergast
Jul 1, 1981·Circulation Research·B F Hoffman, M R Rosen

❮ Previous
Next ❯

Citations

Oct 1, 1994·Pflügers Archiv : European journal of physiology·R Kumar, R W Joyner
Sep 1, 1995·Pflügers Archiv : European journal of physiology·K R SipidoE Carmeliet
Jan 1, 1989·Pflügers Archiv : European journal of physiology·H C Lee, W T Clusin
Feb 1, 1991·Cardiovascular Drugs and Therapy·S G PrioriP J Schwartz
Feb 25, 2010·Pflügers Archiv : European journal of physiology·Matthew J Betzenhauser, Andrew R Marks
Oct 22, 2013·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Wen-Long WangJia-Gao Lv
Jan 30, 1995·Forensic Science International : Synergy·A F RumpW Klaus
May 1, 1989·Journal of the American College of Cardiology·D P Zipes
Jun 1, 2005·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Eugene PattersonRalph Lazzara
Mar 1, 2006·Progress in Biophysics and Molecular Biology·Fabien BretteLaurent Sallé
Oct 24, 1998·Progress in Biophysics and Molecular Biology·E Carmeliet, K Mubagwa
Aug 23, 2001·The Journal of Nutritional Biochemistry·W R. LeifertE J. McMurchie
Nov 13, 2004·The Journal of Nutritional Biochemistry·W R LeifertE J McMurchie
Oct 16, 2013·Journal of Medicinal Chemistry·Chris D SmithThomas G Back
Mar 31, 2009·Nature Medicine·Hiroshi WatanabeBjörn C Knollmann
Aug 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Dawei JiangS R Wayne Chen
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·E MarbanV P Chacko
Apr 27, 2013·Cardiovascular Research·Zhilin QuJames N Weiss
Jun 12, 2013·Cardiovascular Research·John C ShryockLuiz Belardinelli
Oct 1, 2010·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Iori NagaokaMinoru Horie
Mar 1, 1996·Journal of Cardiovascular Pharmacology·E DrouinC Gauthier
Oct 8, 1999·Journal of Cardiovascular Pharmacology·C M GodoyJ W Bassani
Jun 7, 2006·Current Opinion in Cardiology·Dawood Darbar, Dan M Roden
May 20, 1998·Clinical and Experimental Pharmacology & Physiology·S F BroschP Heistracher
Feb 1, 2006·Clinical and Experimental Pharmacology & Physiology·Livia C Hool
Apr 1, 1994·Journal of Cardiovascular Electrophysiology·Z MingR S Aronson
Jun 1, 1997·Journal of Cardiovascular Electrophysiology·E PattersonR Lazzara
Oct 24, 1998·Journal of Cardiovascular Electrophysiology·A Burashnikov, C Antzelevitch
Oct 12, 1999·Journal of Cardiovascular Electrophysiology·M R RosenR Z Gainullin
Jun 9, 2000·Annual Review of Physiology·J Jalife
Feb 5, 2002·Annual Review of Physiology·Dan M RodenMark E Anderson
Aug 20, 2010·American Journal of Physiology. Cell Physiology·Kai GuoBlaise Z Peterson
Mar 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Qunying YuanEvangelia G Kranias
Feb 7, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Zhenghang ZhaoLai-Hua Xie
Jun 15, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Martin FinkDenis Noble
May 10, 2008·Circulation Research·Mark Warren, Alexey V Zaitsev

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.