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Extracellular Adenosine Triphosphate Triggers Arrhythmias and Elemental Redistribution in Electrically Stimulated Rat Cardiac Myocytes

Published online by Cambridge University Press:  02 February 2002

Bin-Xian Zhang ,
Russell W. Desnoyer  and
Meredith Bond
Bin-Xian Zhang
Affiliation:
Department of Molecular Cardiology, NB50, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Russell W. Desnoyer
Affiliation:
Department of Molecular Cardiology, NB50, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Meredith Bond*
Affiliation:
Department of Molecular Cardiology, NB50, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, 2106 Abington Road, Cleveland, OH 44195
*
*Corresponding author
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Abstract

An increase in extracellular adenosine triphosphate (ATP) is arrhythmogenic in rat cardiac myocytes and extracellular ATP levels are elevated during cardiac ischemia. To gain insight into the mechanism by which the arrhythmic contractions are generated, we investigated changes in subcellular elemental content by electron probe microanalysis (EPMA) in isolated adult rat cardiac myocytes stimulated by the ATP analog, 2-methylthio- ATP (2-M-S-ATP). We also measured the effects of 2-M-S-ATP stimulation on myocyte cell shortening. In electrically stimulated myocytes, 2-M-S-ATP stimulation generated arrhythmic contractions and also increased the amplitude of cell shortening. However, only the arrhythmic contractions were reversed by 2-MS- ATP washout. EPMA of freeze-dried cryosections of rapidly frozen 2-M-S-ATP-stimulated myocytes showed increased cytosolic Na and Cl, decreased K, but no significant change in mitochondrial Ca upon 2-M-S-ATP stimulation. The arrhythmias were abolished upon 2-M-S-ATP washout, and the observed changes in cytosolic elemental content also reversed upon agonist washout, thus suggesting that the increased Na and Cl, and decreased K, are specifically associated with the ATP-dependent spontaneous contractile activity. The observed increase in intracellular Na upon 2-M-S-ATP stimulation may explain our observation of prolonged relaxation time of 2-M-S-ATP-stimulated contractions. This may be due to inhibition of Ca2+ efflux via the Na+ Ca2+ exchanger.

Keywords

P2 purinergic receptorarrhythmiascytoplasmic Naelectron probe microanalysiselectron probe microanalysiscardiac myocytesCa2+Na+
Type
Research Article
Information
Microscopy and Microanalysis , Volume 7 , Issue 1 , January 2001 , pp. 48 - 55
Copyright
Copyright © Microscopy Society of America 2001

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Footnotes

B.-X. Zhang is now at Research Service 151, Audie L. Murphy Hospital Division, 7400 Merton Minter Boulevard, San Antonio, TX 78284.