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.
Taylor
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SC
Institute for Cardiovascular Research, University of Leeds, England, UK.
Peers
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C
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004594:Electrophysiology; D005089:Exocytosis / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002110:Caffeine; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D009543:Nifedipine; D010455:Peptides; D011188:Potassium; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA