Extracellular ATP has a potent effect to enhance cystolic calcium and contractility in single ventricular myocytes

Robert S. Danziger, Stefano Raffaeli, Rafael Moreno-Sanchez, Makoto Sakai, Maurizio C. Capogrossi, Harold A. Spurgeon, Richard G. Hansford, Edward G. Lakatta

Research output: Contribution to journalArticle

Abstract

The effect of extracellular ATP on the contraction of single rat cardiac myocytes was investigated, together with the effect on the transient change in cytosolic Ca2+ (Cai) elicited by excitation and on the relationship between these two parameters. In unstimulated single myocytes, ATP caused a small increase in Cai (measured as the ratio of fluorescence of indo-1 at 410 to that at 490 nm. In myocytes bathed in a medium containing 1.0 mM [Ca2+] at 23°C and stimulated at 1 Hz, ATP (1 μM) resulted in a two-threefold increase in amplitude of contraction, as measured by video cinemicrographic techniques. The duration of the Cai-transient was not altered but its amplitude was markedly enhanced, as was the amplitude of contraction. The relation between Cai and contraction-amplitude was not altered by ATP, when measured over a range of extracellular [Ca2+], suggesting that ATP does not affect the myofilament-Ca2+ interaction. The primary site of action of ATP in increasing Cai is at the sarcolemma since the addition to suspensions of myocytes of caffeine (10mM), which depletes the sarcoplasmic reticulum Ca2+ load, does not prevent the subsequent increase of Cai due to ATP. Further, lowering of the extracellular [Ca2+] to less than 1 μM with EGTA abolishes the response of Cai to ATP, though not the response to caffeine. Thus in rat cardiac myocytes ATP stimulates trans-sarcolemmal influx of Ca2+: ADP, AMP and adenosine are ineffective. ATP markedly augments the amplitude of the Cai transient elicited by electrical stimulation thus rendering it a potent inotropic agent.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalCell Calcium
Volume9
Issue number4
DOIs
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

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    Danziger, R. S., Raffaeli, S., Moreno-Sanchez, R., Sakai, M., Capogrossi, M. C., Spurgeon, H. A., Hansford, R. G., & Lakatta, E. G. (1988). Extracellular ATP has a potent effect to enhance cystolic calcium and contractility in single ventricular myocytes. Cell Calcium, 9(4), 193-199. https://doi.org/10.1016/0143-4160(88)90023-1