Extracellular ATP activates coordinated Na+, Pi, and Ca2+ transport in cardiac myocytes.
Activation of an ATP receptor has previously been shown to induce cytosolic [Ca2+] transients in rat ventricular myocytes. A slower but larger [Ca2+] increase which can cause cell hypercontraction follows the transient when extracellular Pi is increased. This second phase of the [Ca2+] response is stimulated by ATP or adenosine 5'-(gamma-thio)triphosphate in a medium containing 11.2 mM Pi, but not by high concentrations of 2-methylthio-ATP, which stimulate only the initial [Ca2+] transient. Replacing medium Na+ with N-methyl-D-glucamine suppresses this Pi-dependent [Ca2+] increase following ATP addition, suggesting a causal relationship between Na+ transport and Ca2+ influx. Blocking voltage-sensitive Na+ channels, Na(+)-H+ exchange, or Na(+)-K(+)-Cl- cotransport did not reduce ATP-induced cell hypercontraction in 11.2 mM Pi medium, suggesting that these transporters are not involved. ATP stimulation of Na(+)-Pi cotransport was investigated with isotopic methods. The results were consistent with the hypothesis that extracellular ATP stimulates Na(+)-Pi cotransport, which activates Na(+)-Ca2+ exchange. A novel Pi-dependent ATP receptor-effector system has been demonstrated in cardiac cells, and it may have significant effects on cellular transport, contractility, and bioenergetics.
De Young
M B
MB
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Scarpa
A
A
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D010710:Phosphates; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium; D016257:Fura-2