Cell Calcium (1988) 9, 193-199 t Longman Group UK Ltd 1988 Extracellular ATP has a potent cystolic calcium and contractility ventricular myocytes effect to enhance In single ROBERT S DANZIGER, STEFANO RAFFAELI, RAFAEL MORENO-SANCHEZ, MAKOTO SAKAI, MAURI210 C CAPOGROSSI, HAROLD A SPURGEON, RICHARD G HANSFORD, and EDWARD G LAKATTA zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Laboratory of Cardiovascular Science, Gerontology Research Center, National lnsfitute on Aging, National Institutes of Health, Baltimore, USA Abstract - The effect of extracellular ATP on the contraction of single mt cardiac my+ocytes was Investigated, together with the effect on the transient change In cytorolrc Ca (W ellclted by excltatlon and on the rebtlonshlp between these two parameters. In unettmukted single myocytes, ATP caused a rmail increase in zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI Cm (measured zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM as the ratio of fluorescence of Indo-l at 410 to that at 490 nm. In myocytes bathed in a medium containing 1.0 mM [Ca*+] at 23% and stimulated at 1 Hz, ATP (1 @II) resulted in a two-threefokf increase in amplftude of contraction, as measured by video cinemicrographic techniques. The duration of the Cri-tran- sient was not altered but its amplitude was markedly enhanced, as was the amplitude of con- traction. 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 myofi- lament-Ca*+ interaction. The primary site of action of ATP in increasing Cai is at the sarco- Iemma since the addition to suspensions of myocytes of caffeine (IOmM), which depktea the sarcopkrmlc reticulum Ca2 + load, does not prevent the a&sequent Mrease of Cal due to ATP. Further, lowering of the extracdlulrr [Ca*+] to lesr than 1 bM with EGTA abolishes the response of Car to ATP, though not the reaponre to caffeine. Thus in rat cardiac myocytes ATP stimulates trans-sarcolemmal influx of Ca*+ : ADP, AMP and adenoslne are Ineffective. ATP markedly augments the amplitude of the Cai transient elicited by electrical st,tlmuIation thus rendering it a potent inotropic agent. Recent evidence suggests that ATP is released dur- inositol phosphate accumulation and Ca3+ mobili- ing neural stimulalion of many lissues 11, 21 includ- zalion in primary cullures of ral aortic myocytes [9] ing rat tail artery 13). guinea pig taenia coli 14) and and induce the release of prostaglandins from per- vas deferens [_‘J. Extracellular ATP stimulates P2 fused vascular beds and isolated blood vessels [IO- purine receptors [O] and is known to regulate vas- 14) and pig or bovine aorta [ 12, 14J. cular smooth muscle tone 171, raise cytosolic free Ca’+ - ATP is released from some nerve terminals as a III piglet aortic endothelial cells [8], stimulate co-transmitter with norepinephrine [15-171 and, in- 193