Store‐Operated Ca2+ Influx and Voltage‐Gated Ca2+ Channels Coupled to Exocytosis in Pheochromocytoma (PC12) Cells

: Microamperometry was used to monitor quantal catecholamine release from individual PC12 cells in response to raised extracellular K+ and caffeine. K+‐evoked exocytosis was entirely dependent on Ca2+ influx through voltage‐gated Ca2+ channels, and of the subtypes of such channels present in these cells, influx through N‐type was primarily responsible for triggering exocytosis. L‐type channels played a minor role in mediating K+‐evoked secretion, whereas P/Q‐type channels did not appear to be involved in secretion at all. Caffeine also evoked catecholamine release from PC12 cells, but only in the presence of extracellular Ca2+. Application of caffeine in Ca2+‐free solutions evoked large, transient rises of [Ca2+]i, but did not trigger exocytosis. When Ca2+ was restored to the extracellular solution (in the absence of caffeine), store‐operated Ca2+ influx was observed, which evoked exocytosis. The amount of secretion evoked by this influx pathway was far greater than release triggered by influx through L‐type Ca2+ channels, but less than that caused by Ca2+ influx through N‐type channels. Our results indicate that exocytosis may be regulated even in excitable cells by Ca2+ influx through pathways other than voltage‐gated Ca2+ channels.