Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion.

Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion.
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二氢吡啶敏感的 Ca2+ 通道在 Ca(2+) 诱导的降钙素分泌中的主要作用。

DOI:
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发表时间:
1993
影响因子:
--
通讯作者:
J. Hescheler
J. Hescheler
中科院分区:
--
文献类型:
--
作者:
H. Scherübl;T. Kleppisch;A. Zink;F. Raue;D. Krautwurst;J. Hescheler

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已知内分泌细胞具有多种类型的Ca 2+通道。在神经元中,ω-芋螺毒素敏感的N-型Ca 2+通道已被证明在神经递质释放中起主导作用,但在内分泌细胞中参与刺激-分泌偶联的Ca 2+通道的类型仍不确定。我们研究了甲状腺滤泡旁细胞(C细胞)中1,4-二氢吡啶敏感性和ω-芋螺毒素敏感性Ca 2+通道对Ca(2+)诱导的降钙素释放的相对贡献。在全细胞电压钳实验中,鉴定了1,4-二氢吡啶敏感性和ω-芋螺毒素敏感性Ca 2+通道电流。二氢吡啶isradipine(1 μ M),但不ω-芋螺毒素(1 μ M)抑制稳态Ca 2+流入生理膜电位,自发电活动,降钙素分泌(在2小时孵育)。此外,抑制自发电活动的Na+通道阻滞剂河豚毒素不影响降钙素的释放。我们的结论是,1,4-二氢吡啶敏感的钙通道在钙依赖性降钙素释放中起主要作用,即使在没有动作电位的情况下,由于钙内流的降钙素分泌也在进行。
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.
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