Calmodulin antagonist W-7 prevents sparfloxacin-induced early afterdepolarizations (EADs) in isolated rabbit purkinje fibers: importance of beat-to-beat instability of the repolarization

Journal of Cardiovascular Electrophysiology
Hua Rong LuDavid J Gallacher

Abstract

The occurrence of early afterdepolarizations (EADs) has been related to the incidence of torsades de pointes in drug-induced long QT (LQT). The generation of EADs may be facilitated by Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase). In the present study, we investigated a possible involvement of Ca(2+)/Calmodulin dependent protein kinase in the generation of sparfloxacin-induced EADs in isolated rabbit Purkinje fibers by means of a calmodulin antagonist W-7. EADs were evident in 8 of the 10 preparations perfused with sparfloxacin at 1 x 10(-4) M and stimulated at 0.2 Hz. The induction of EADs by sparfloxacin was associated with a large prolongation of the duration of the action potential (APD), an increase in the triangulation, and the short-term instability of the repolarization. CaM kinase blockade with the calmodulin antagonist W-7 inhibited sparfloxacin-induced EADs in a concentration-dependent manner (EADs were induced in 3 of 10, 1 of 10, and 0 of 8 preparations in the presence of W-7 at 5 x 10(-7) M, 5 x 10(-6) M, and 5 x 10(-5) M, respectively; P < 0.01 at 5 x 10(-6) M and 5 x 10(-5) M). The inhibition of sparfloxacin-induced EADs by W-7 at 5 x 10(-7) M and 5 x 10(-6) M was associated with a significant decr...Continue Reading

References

Jun 1, 1984·Journal of the American College of Cardiology·E SchechterR Lazzara
Apr 1, 1996·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·H DupontB Regnier
Jun 1, 1997·Journal of Cardiovascular Electrophysiology·E PattersonR Lazzara
Jan 31, 1998·Science·P De Koninck, H Schulman
Apr 2, 1998·Fundamental & Clinical Pharmacology·M M AdamantidisR Bordet
Jun 11, 1999·The American Journal of Physiology·Y WuM E Anderson
Jul 6, 2000·The EMBO Journal·R SchönherrS H Heinemann
Oct 21, 2000·European Journal of Pharmacology·U BischoffO Pongs
Sep 13, 2003·European Journal of Pharmacology·Akira TakaharaKeitaro Hashimoto
Nov 19, 2003·American Journal of Therapeutics·Luigi X Cubeddu
Feb 6, 2004·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Rashmi R Shah
Jun 5, 2004·Trends in Cardiovascular Medicine·Mark E Anderson
Jan 18, 2005·Journal of the American College of Cardiology·Takeshi AibaKenji Sunagawa
Jun 7, 2005·Journal of Pharmacological and Toxicological Methods·H van der LindeD J Gallacher
Jun 28, 2005·Journal of Pharmacological and Toxicological Methods·Hua Rong LuDavid J Gallacher

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Citations

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
Jul 4, 2009·Expert Opinion on Drug Metabolism & Toxicology·Emanuel RaschiMaurizio Recanatini
Jul 14, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Gudrun Antoons, Morten B Thomsen
Mar 11, 2008·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Emanuel RaschiFabrizio De Ponti
Apr 15, 2008·Drug Discovery Today·Wolfgang MusterAxel Pähler
Dec 5, 2006·Current Opinion in Cardiology·Prince J Kannankeril, Dan M Roden
Jan 16, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Yu-Jie QuMichael J Morales
Dec 5, 2006·Current Opinion in Cardiology

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