Extracellular ATP activates coordinated Na+, Pi, and Ca2+ transport in cardiac myocytes

• Published in: The American journal of physiology Vol. 260; no. 6 Pt 1; pp. C1182 - C1190
• Main Authors: De Young, M B, Scarpa, A
• Format: Journal Article
• Language: English
• Published: United States 01-06-1991
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Biological Transport - drug effects; Calcium - metabolism; Cells, Cultured; Cytosol - metabolism; Fura-2; Kinetics; Myocardium - cytology; Myocardium - metabolism; Phosphates - metabolism; Rats; Sodium - metabolism; Spectrometry, Fluorescence
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1991.260.6.C1182

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.