Mechanism of ATP-induced Ca2+ efflux from freshly isolated adult rat cardiomyocytes: possible involvement of Na+/Ca2+ exchange
Hori, T.; Yoshizumi, M.; Kitagawa, T.; Houchi, H.; Oka, M.; Katoh, I.
Tokushima Journal of Experimental Medicine 43(3-4): 127-134
1996
ISSN/ISBN: 0040-8875 PMID: 9100461 Document Number: 464322
Physiological stimulation causes a rise in intracellular Ca-2+ concentration in cardiomyocytes. However, it has not yet been elucidated what mechanisms are involved in the reduction of cytosolic free Ca-2+ levels, including those which underlie Ca-2+ efflux from the cells. In the present study, we examined the effect of extracellular adenosine 5'-triphosphate (ATP) on Ca-2+ efflux from freshly isolated adult rat cardiomyocytes. The isolated cardiomyocytes were preloaded with 45CaCl-2 for one hour. Then, the fractional release of 45Ca-2+ from the cells was measured consecutively. ATP stimulated the efflux of 45Ca-2+ from isolated adult rat cardiomyocytes in a concentration-dependent manner (0.01-1 mM). The 45Ca-2+ efflux from the cells was also stimulated by adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma-s), alpha, beta-methylene-ATP and adenosine 5'-diphosphate (ADP), but not by adenosine 5'-monophosphate (AMP) or adenosine. The effect of ATP was inhibited by a specific purinergic P-2-receptor antagonist, but not by a P-1-receptor antagonist. From these results, it is conceivable that the effect of ATP on Ca-2+ efflux from cardiomyocytes is mediated through P-2-purinoceptors. The ATP-stimulated 45Ca-2+ efflux was not affected by removal of extracellular Ca-2+, but was dependent on the presence of extracellular Na+. Moreover, ATP caused a 22Na+ influx into the cells. These results suggest that ATP stimulates extracellular Na+-dependent 45Ca-2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on plasma membrane P-2-purinoceptors which may couple to Na+/Ca-2+ exchange.