MULTIPLE PATHWAYS FOR ATP-INDUCED INTRACELLULAR CALCIUM ELEVATION IN PHEOCHROMOCYTOMA (PC12) CELLS

Extracellular ATP excites neurons in both the peripheral and central n ervous system. To elucidate the mechanisms involved, we used spectrofl uorometric analysis to study the pathways by which extracellular ATP e levates the intracellular Ca2+ concentration ([Ca2+](i)) in individual , fura-2-loaded, rat pheochromocytoma PC12 cells. ATP (>1 mu M) increa sed [Ca2+](i). The ATP effect on [Ca2+](i) was completely abolished by a nominally Ca2+-free extracellular medium, which indicates that the ATP-induced increase in [Ca2+](i) was due to an influx of extracellula r Ca2+. We next applied specific blockers of voltage-dependent Ca2+ ch annels and used experimental protocols with depolarizing external K+-r ich solutions. Our results show that ATP induces influx of extracellul ar Ca2+ through (a) dihydropyridine-sensitive (L(n)-type) Ca2+ channel s, (b) Ca2+-permeable, voltage-independent, Cd2+-insensitive cation ch annels, and (c) an as yet unidentified, voltage-dependent, Cd2+-sensit ive Ca2+ influx system.