EFFECT OF EXTRACELLULAR ATP ON THE NA+ CURRENT IN RAT VENTRICULAR MYOCYTES

Extracellular ATP concentration can rise because of its release by ner ve terminals and by damaged cells during ischemia. After the activatio n of P2-purinergic receptors, ATP induces a positive inotropic effect and increases the L-type Ca2+ current via activation of a G(s) protein but without cAMP production. In addition, ATP shifts the voltage char acteristics of Ca2+ current toward hyperpolarized potentials. If ATP p roduced similar effects on the Na+ current (I(Na)), this compound shou ld also affect cardiac excitability and conduction. Using the whole-ce ll patch-clamp to record I(Na) in rat ventricular cells, we show that extracellular application of ATP induced hyperpolarizing shifts in the current-voltage relation and the availability of I(Na). The ED50 for the shifts in both conductance and availability was obtained with 0.7 mumol/L ATP. Maximal shifts in conductance and availability were respe ctively 9.7+/-0.6 and 10.6+/-0.7 mV. The leftward shift of the availab ility curve is responsible for the decrease of I(Na) amplitude at less polarized holding potentials. These effects were not cholera toxin se nsitive and thus cannot be attributed to activation of the G(s) protei n. At 100 mumol/L, ATPgammaS and alpha,beta-methylene ATP could induce shift, whereas UTP and beta,gamma-methylene ATP as well as ADP and ad enosine were without effect. Thus, depending on the resting membrane p otential, ATP should either enhance excitability or favor slow conduct ion and weaken cardiac electrical homogeneity and consequently favor a rrhythmia.