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

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⁺ (Ca_i) elicited by excitation and on the relationship between these two parameters. In unstimulated single myocytes, ATP caused a small increase in Ca_i (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 Ca_i-transient was not altered but its amplitude was markedly enhanced, as was the amplitude of contraction. The relation between Ca_i 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 Ca_i 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 Ca_i due to ATP. Further, lowering of the extracellular [Ca²⁺] to less than 1 μM with EGTA abolishes the response of Ca_i 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 Ca_i transient elicited by electrical stimulation thus rendering it a potent inotropic agent.