Major role of dihydropyridine-sensitive Ca²⁺ channels in Ca²⁺-induced calcitonin secretion

Endocrine cells are known to possess multiple types of Ca²⁺ channels. In neurons, ω-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 ω-conotoxin-sensitive Ca²⁺ channels to Ca²⁺-induced calcitonin release in parafollicular cells of the thyroid (C cells). In whole cell voltage-clamp experiments, both 1,4-dihydropyridine- sensitive and ω-conotoxin-sensitive Ca²⁺ channel currents were identified. The dihydropyridine isradipine (1 μM) but not ω-conotoxin (1 μM) 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 Ca²⁺-dependent calcitonin release and that calcitonin secretion due to Ca²⁺ influx proceeds even in the absence of action potentials.