Multiple Pathways for ATP-lnduced Intracellular Calcium Elevation in Pheochromocytoma (PC12) Cells

Abstract

Extracellular ATP excites neurons in both the peripheral and central nervous system. To elucidate the mechanisms involved, we used spectrofluorometric analysis to study the pathways by which extracellular ATP elevates the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in individual, fura-2-loaded, rat pheochromocytoma PC12 cells. ATP ( > 1 µM) increased [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 extracellular Ca²⁺. We next applied specific blockers of voltage-dependent Ca²⁺ channels and used experimental protocols with depolarizing external K⁺-rich solutions. Our results show that ATP induces influx of extracellular Ca²⁺ through (a) dihydropyridine-sensitive (L_n-type) Ca²⁺ channels, (b) Ca²⁺-permeable, voltage-independent, Cd²⁺-insensitive cation channels, and (c) an as yet unidentified, voltage-dependent, Cd²⁺-sensitive Ca²⁺ influx system.

Cyanidin-3-glucoside Inhibits ATP-induced Intracellular Free Ca2+Concentration, ROS Formation and Mitochondrial Depolarization in PC12 Cells

“…Since the L-type and N-type Ca 2+ channels are expressed in the PC12 cells [26], we tested whether cyanidin-3-glucoside affects the ATP-induced secondary Ca 2+ influx through voltage-gated L-type and N-type Ca 2+ channels (Fig. 4).…”

Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways

“…In PC12 cells, ATP induces Ca 2＋ influx through the secondary activation of voltage-gated Ca 2＋ channels following depolarization of the membrane by the ATP-induced activation of non-selective cation channels [34]. In addition to L-type voltage-dependent Ca 2＋ channels, it has been reported that ATP can induce a [Ca 2＋ ]i increase in PC12 cells through dihydropyridine-and CTXinsensitive-voltage-dependent Ca 2＋ channels [34]. In this study, octyl gallate inhibited high KCl-induced [Ca 2＋ ]i increase.…”