Nicotine induces calcium spikes in single nerve terminal varicosities: A role for intracellular calcium stores
Nicotine induces calcium spikes in single nerve terminal varicosities: A role for intracellular calcium stores
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DOI：
10.1016/s0306-4522(01)00280-9
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Cunnane, TC
中科院分区：
文献类型：
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作者：
Brain, KL;Trout, SJ;Cunnane, TC
虽然已知尼古丁作用于神经元烟碱型乙酰胆碱受体(NAChRs)以促进神经递质的释放，但其机制尚不清楚。已知它的一些作用是由突触前受体介导的。在小鼠输精管中，尼古丁(10-30微米)使神经源性收缩强度瞬间增加135+/-25%，兴奋性连接电位的幅度增加74+/-6%，自发兴奋性连接电位的频率增加。用共聚焦显微镜和钙指示剂Oregon Green 488 BAPTA-1葡聚糖检测神经末梢钙离子浓度的变化。尼古丁不影响动作电位诱发的钙瞬变，而是以0.09+/-0.02赫兹的平均频率触发静脉曲张内钙浓度的小而随机波动(钙峰)。这些细胞对河豚毒素在阻断动作电位诱发的钙瞬变(300 NM)的浓度下不敏感。它们被nAChR阻滞剂六甲溴铵(100um)、兰尼定(100um)和咖啡因(3 MM)所消除，这两种药物都能改变细胞内钙释放。我们提出了一种新的机制，尼古丁在nAChRs上的作用触发了钙诱导神经末梢对兰尼定敏感的钙库的钙释放。这启动了神经递质释放机制，并增强了自发和动作电位诱发的神经递质释放。(C)2001年IBRO。爱思唯尔科学有限公司出版。版权所有。
While nicotine is known to act at neuronal nicotinic acetylcholine receptors (nAChRs) to facilitate neurotransmitter release, the mechanisms underlying this action are poorly understood. Some of its effects are known to be mediated by presynaptic receptors. In the mouse vas deferens nicotine (10-30 muM) transiently increased the force of neurogenic contraction by 135 +/- 25%, increased the amplitude of excitatory junction potentials by 74 +/- 6% and increased the frequency of spontaneous excitatory junction potentials in four out of six preparations. Confocal microscopy and the calcium indicator Oregon Green 488 BAPTA-1 dextran were used to measure calcium concentration changes in the nerve terminals. Nicotine did not affect the action potential-evoked calcium transient but instead triggered small, random fluctuations ('calcium. spikes') in intra-varicosity calcium concentrations at an average frequency of 0.09 +/- 0.02 Hz. These were insensitive to tetrodotoxin at a concentration that blocked action-potential evoked calcium transients (300 nM). They were abolished by the nAChR blocker hexamethonium (100 muM) and by both ryanodine (100 muM) and caffeine (3 mM), agents that modify calcium release from intracellular stores. We propose a novel mechanism whereby nicotine's action at nAChRs triggers calcium-induced calcium release from a ryanodine-sensitive calcium store in nerve terminals. This primes neurotransmitter release mechanisms and enhances both spontaneous and action potential-evoked neurotransmitter release. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.