Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion.
Endocrine cells are known to possess multiple types of Ca2+ channels. In neurons, omega-conotoxin-sensitive N-type Ca2+ channels have been shown to play a dominant role in neurotransmitter release, but uncertainty remains about the types of Ca2+ channels involved in stimulus-secretion coupling in endocrine cells. We investigated the relative contribution of 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channels to Ca(2+)-induced calcitonin release in parafollicular cells of the thyroid (C cells). In whole cell voltage-clamp experiments, both 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channel currents were identified. The dihydropyridine isradipine (1 microM) but not omega-conotoxin (1 microM) inhibited the steady-state Ca2+ influx at physiological membrane potentials, the spontaneous electrical activity, and calcitonin secretion (at 2-h incubations). Moreover, suppression of the spontaneous electrical activity by the Na+ channel blocker tetrodotoxin did not affect calcitonin release. We conclude that 1,4-dihydropyridine-sensitive Ca2+ channels play a major role in Ca(2+)-dependent calcitonin release and that calcitonin secretion due to Ca2+ influx proceeds even in the absence of action potentials.
Pharmakologisches Institut, Freie Universität Berlin, Germany.
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Scherübl
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Kleppisch
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Zink
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Raue
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Krautwurst
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Hescheler
D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D017275:Isradipine / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D013779:Tetrodotoxin; D002116:Calcitonin; D002118:Calcium; D017275:Isradipine