Membrane depolarization combined with release of calcium from internal stores does not trigger secretion from PC 12 cells.

The mechanisms underlying catecholamine release from pheochromocytoma (PC 12) cells were examined. Whereas application of 1 microM bradykinin (BK) induced an increase in intracellular calcium ([Ca2+])i), either in medium containing 1.8 mM Ca2+ or in medium prepared without the addition of CaCl2 ("Ca(2+)-free medium"), norepinephrine ([3H]NE) release was induced only in Ca(2+)-containing medium. Similarly depolarization by 50 mM potassium induced [3H]NE release only in 1.8 mM calcium-containing medium. The combination of membrane depolarization (50 mM KCl) with increased [Ca2+]i secondary to BK application in "Ca(2+)-free medium" did not induce catecholamine secretion. It was concluded that Ca2+ entry through calcium channels at the plasma membrane is essential for the activation of catecholamine release. A rise in [Ca2+]i (4-5 times x basal) released from internal stores is not sufficient to trigger secretion from PC 12 cells, either by itself or in combination with membrane depolarization.