Ca2+ flux and signaling implications by nicotinic acetylcholine receptors in rat medial habenula.
Ca2+ flux and signaling implications by nicotinic acetylcholine receptors in rat medial habenula.
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DOI：
10.1152/jn.01046.2005
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发表时间：
2007
影响因子：
2.5
通讯作者：
Xiaochuan Guo;R. Lester
中科院分区：
文献类型：
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作者：
Xiaochuan Guo;R. Lester
通过同时监测激动剂诱导的膜电流和细胞内[Ca(2+)]的实验，计算了急性分离的大鼠内侧缰核(MHB)神经元上通过烟碱型乙酰胆碱受体(NAChRs)的Ca(2+)(Fca(2+))携带的内向电流的比例。在-50 mV的细胞外钙离子(2 MM)的生理浓度下，钙离子携带电流的百分比约为3-4%，这与外周组织中表达的其他异构型烟碱受体的测量结果非常一致。在可能影响这一测量的因素中，如通过电压门控Ca(2+)通道的Ca(2+)内流，细胞内Ca(2+)缓冲液的浓度，以及Ca(2+)从细胞内的储存和释放，只有线粒体摄取的Ca(2+)显示了混淆的分析。此外，我们还发现，由于MHB细胞上nAChRs的密度很高，低浓度的ACh(10微米)及其水解物胆碱(1 MM)可以显著升高细胞内钙离子。此外，在nAChRs持续激活过程中，细胞内钙离子浓度在生理范围内与细胞外钙离子浓度成正比。综上所述，这些发现支持nAChRs可能能够感觉到低浓度的弥漫性释放的神经递质，此外，通过细胞外钙(2+)的变化来传递关于正在进行的局部突触活动的信息。
The fraction of inward current carried by Ca(2+) (FCa(2+)) through nicotinic acetylcholine receptors (nAChRs) on acutely isolated rat medial habenula (MHb) neurons was calculated from experiments that simultaneously monitored agonist-induced membrane currents and intracellular [Ca(2+)], measured with patch-clamp and indo-1 fluorescence, respectively. In physiological concentrations of extracellular Ca(2+) (2 mM) at -50 mV, the percentage of current carried by Ca(2+) was determined to be roughly 3-4%, which is in close agreement with measurements from other heteromeric nicotinic receptors expressed in peripheral tissue. Among factors that may have affected this measurement, such as Ca(2+) influx through voltage-gated Ca(2+) channels, the concentration of intracellular Ca(2+) buffer, and Ca(2+) sequestration and release from intracellular stores, only Ca(2+) uptake by mitochondria was shown to confound the analysis. Furthermore, we find that because of the high density of nAChRs on MHb cells, low concentrations of ACh (10 microM) and its hydrolysis product, choline (1 mM), can significantly elevate intracellular Ca(2+). Moreover, during persistent activation of nAChRs, the level of intracellular Ca(2+) is proportional to its extracellular concentration in the physiological range. Together, these findings support the suggestion that nAChRs may be capable of sensing low concentrations of diffusely released neurotransmitter and, in addition, transfer information about ongoing local synaptic activity by changes in extracellular Ca(2+).