Effects of SEA0400 on Ouabain-induced Arrhythmias in Guinea Pigs

Authors

  • M. S. Amran Dhaka University
  • N. Homma University of Yamanashi
  • K. Hashimoto University of Yamanashi

DOI:

https://doi.org/10.3329/jsr.v4i1.7722

Keywords:

Na -Ca2 exchange (NCX), SEA0400, NCX inhibitors, current clamp, ECG.

Abstract

The sodium-calcium exchange (NCX) is one of the major regulators of intracellular Ca2+ concentration in cardiac myocytes. The effects of NCX blockers as antiarrhythmic agents are still controversial. We investigated antiarrhythmic effects of SEA0400 (SEA), a novel NCX inhibitor, on ouabain-induced arrhythmias in guinea pigs. In the whole animal arrhythmia model, we observed effects of SEA on the ouabain-induced arrhythmia using ECG recordings. In the isolated myocyte, we observed action potential configurations and oscillations due to calcium overload using the current clamp method. In the whole animal model, SEA at a dose range of 1-10 mg/kg (intravenous, bolus) suppressed ouabain-induced arrhythmias dose-dependently. In isolated ventricular myocytes, SEA (0.1-3 µM) suppressed ouabain-induced oscillatory activity observed between action potentials. SEA (0.1-3 µM) also suppressed ouabain-induced NCX current (INCX) that is also called transient inward current (ITI). Our results indicate that NCX is involved in arrhythmia and oscillatory activity induced by ouabain. The inhibition of these arrhythmias and oscillatory activity by SEA might result from the inhibition of NCX.

Keywords: Na+-Ca2+ exchange (NCX); SEA0400; NCX inhibitors; current clamp; ECG.

© 2012 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.

doi: http://dx.doi.org/10.3329/jsr.v4i1.7722

J. Sci. Res. 4 (1), 213-225 (2012)

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Author Biographies

M. S. Amran, Dhaka University

Dr. Md. Shah Amran

Associate Professor

Department of Pharmaceutical Chemistry,

Faculty of Pharmacy,

Dhaka University,

Dhaka-1000, Bangladesh

N. Homma, University of Yamanashi

Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Tamaho, Yamanashi-409-3898, Japan.

K. Hashimoto, University of Yamanashi

Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Tamaho, Yamanashi-409-3898, Japan.

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Published

2011-12-26

How to Cite

Amran, M. S., Homma, N., & Hashimoto, K. (2011). Effects of SEA0400 on Ouabain-induced Arrhythmias in Guinea Pigs. Journal of Scientific Research, 4(1), 213. https://doi.org/10.3329/jsr.v4i1.7722

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Section

Section B: Chemical and Biological Sciences