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 ind ividual PC12 cells in response to raised extracellular K+ and caffeine. K+- evoked exocytosis was entirely dependent on Ca2+ influx through voltage-gat ed Ca2+ channels, and of the subtypes of such channels present in these cel ls, influx through N-type was primarily responsible for triggering exocytos is. L-type channels played a minor role in mediating K+-evoked secretion, w hereas 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 th e presence of extracellular Ca2+. Application of caffeine in Ca2+-free solu tions evoked large, transient rises of [Ca2+](i), but did not trigger exocy tosis. When Ca2+ was restored to the extracellular solution (in the absence of caffeine), store-operated Ca2+ influx was observed, which evoked exocyt osis. The amount of secretion evoked by this influx pathway was far greater than release triggered by influx through L-type Ca2+ channels, but less th an that caused by Ca2+ influx through N-type channels. Our results indicate that exocytosis may be regulated even in excitable cells by Ca2+ influx th rough pathways other than voltage-gated Ca2+ channels.