Scherübl H, Kleppisch T, Zink A, Raue F, Krautwurst D, Hescheler J
Pharmakologisches Institut, Freie Universität Berlin, Germany.
Am J Physiol. 1993 Mar;264(3 Pt 1):E354-60. doi: 10.1152/ajpendo.1993.264.3.E354.
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.
已知内分泌细胞拥有多种类型的钙离子通道。在神经元中，ω-芋螺毒素敏感的N型钙离子通道已被证明在神经递质释放中起主导作用，但关于内分泌细胞中刺激-分泌偶联所涉及的钙离子通道类型仍存在不确定性。我们研究了1,4-二氢吡啶敏感和ω-芋螺毒素敏感的钙离子通道对甲状腺滤泡旁细胞（C细胞）中钙离子诱导的降钙素释放的相对贡献。在全细胞电压钳实验中，鉴定出了1,4-二氢吡啶敏感和ω-芋螺毒素敏感的钙离子通道电流。二氢吡啶伊拉地平（1微摩尔）而非ω-芋螺毒素（1微摩尔）在生理膜电位下抑制了稳态钙离子内流、自发电活动和降钙素分泌（在2小时孵育时）。此外，钠离子通道阻滞剂河豚毒素对自发电活动的抑制并不影响降钙素释放。我们得出结论，1,4-二氢吡啶敏感的钙离子通道在钙离子依赖性降钙素释放中起主要作用，并且即使在没有动作电位的情况下，由于钙离子内流导致的降钙素分泌仍会进行。
