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

An increase in extracellular adenosine triphosphate (ATP) is arrhythmogenic in rat cardiac myocytes and extracellular ATP levels are elevated during c ardiac ischemia. To gain insight into the mechanism by which the arrhythmic contractions are generated, we investigated changes in subcellular element al content by electron probe microanalysis (EPMA) in isolated adult rat car diac myocytes stimulated by the ATP analog, 2-methylthio-ATP (2-M-S-ATP). W e also measured the effects of 2-M-S-ATP stimulation on myocyte cell shorte ning. 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 washo ut. EPMA of freeze-dried cryosections of rapidly frozen 2-M-S-ATP-stimulate d myocytes showed increased cytosolic Na and Cl, decreased K, but no signif icant change in mitochondrial Ca upon 2-M-S-ATP stimulation. The arrhythmia s were abolished upon 2-M-S-ATP washout, and the observed changes in cytoso lic elemental content also reversed upon agonist washout, thus suggesting t hat the increased Na and Cl, and decreased K, are specifically associated w ith the ATP-dependent spontaneous contractile activity. The observed increa se in intracellular Na upon 2-M-S-ATP stimulation may explain our observati on 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.