We have investigated the effects of the calcium-sensitizing inotropic agent EMD 57033 on Ca2+ handling in intact and skinned rat ventricular myocytes. Intracellular Ca2+ was monitored using fura 2. Myocytes were saponin-skinned, allowing study of sarcoplasmic reticulum (SR) function. In intact myocytes EMD 57033 (1–10 µmol/l) produced a concentration-dependent decrease in the amplitude of the Ca2+ transient and prolonged its declining phase, but had no effect on the rise time. In skinned myocytes, the amplitude of spontaneous Ca2+ release from the SR was decreased by EMD 57033 (5 and 10 µmol/l), although this agent had no significant effect on the frequency of spontaneous Ca2+ release. In the presence of the cross-bridge inhibitor 2,3-butanedione monoxime (5 mmol/l), or in a low bathing Ca2+ concentration (1 mmol/l), EMD 57033 (10 µmol/l) had smaller effects on both the amplitude and time course of the Ca2+ transient in intact cells than in the absence of 2,3-butanedione monoxime or in the presence of 2 and 5 mmol/l Ca2+ respectively. These data suggest that the effects of EMD 57033 on Ca2+ are due to changes in Ca2+ binding to troponin C, secondary to cross-bridge formation. Thus, during positive inotropy, EMD 57033 is unlikely to provoke arrhythmias due to effects on SR Ca2+ handling. In intact cells, its effects on Ca2+ handling would be expected to protect against arrhythmias.
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November 23 2000
Effects of the Ca2+ sensitizer EMD 57033 on intracellular Ca2+ in rat ventricular myocytes: relevance to arrhythmogenesis during positive inotropy Available to Purchase
Makoto KAWAI;
Makoto KAWAI
*School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, U.K.
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John A. LEE;
†Department of Pathology, The Medical School, Beech Hill Road, Sheffield S10 2RX, U.K.
Correspondence: Dr J. A. Lee (e-mail [email protected]).
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Clive H. ORCHARD
Clive H. ORCHARD
*School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, U.K.
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Publisher: Portland Press Ltd
Received:
March 08 2000
Revision Received:
July 05 2000
Accepted:
August 15 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (6): 547–554.
Article history
Received:
March 08 2000
Revision Received:
July 05 2000
Accepted:
August 15 2000
Citation
Makoto KAWAI, John A. LEE, Clive H. ORCHARD; Effects of the Ca2+ sensitizer EMD 57033 on intracellular Ca2+ in rat ventricular myocytes: relevance to arrhythmogenesis during positive inotropy. Clin Sci (Lond) 1 December 2000; 99 (6): 547–554. doi: https://doi.org/10.1042/cs0990547
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