Characterization of Na+ influx mediated by ATP(4-)-activated P2 purinoceptors in PC12 cells.

1. Micromolar levels of extracellular ATP increased cytosolic Na+ concentration ([Na+]i) as well as cytosolic Ca2+ concentration ([Ca2+]i) in PC12 cells. 2. Pretreatment of cells with tetrodotoxin, benzamil or thapsigargin did not alter the ATP-induced Na+ influx. 3. Increased extracellular Mg2+ concentration decreased the ATP effect. Furthermore, when the extracellular ATP pool was treated to contain corresponding calculated concentrations of ATP4-, the increase in [Na+]i stayed linked to the ATP4- concentration rather than to the total ATP concentrations in the stimulants. 4. Extracellular ATP does not create nonselective pores as shown by the fact that ethidium bromide does not enter the cells upon ATP stimulation. 5. Among the tested nucleotides, only adenosine 5'-O-(3-thiotriphosphate), 2-methylthio ATP and 2-chloro ATP also caused Na+ influx. 6. Reactive Blue 2 specifically decreased the ATP effect in a concentration-dependent manner. 7. The results suggest that extracellular ATP triggers Na+ influx through a P2 purinoceptor which is activated by ATP4- in PC12 cells.