Extracellular adenosine triphosphate triggers arrhythmias and elemental redistribution in electrically stimulated rat cardiac myocytes

Bin Xian Zhang, Russell W. Desnoyer, Meredith Bond

Research output: Contribution to journalArticle

4 Scopus citations

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-M-S-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.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalMicroscopy and Microanalysis
Volume7
Issue number1
StatePublished - Jan 1 2001

Keywords

  • Arrhythmias
  • Ca
  • Cardiac myocytes
  • Cytoplasmic Na
  • Electron probe microanalysis
  • Na
  • P purinergic receptor

ASJC Scopus subject areas

  • Instrumentation

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