NAADP-mediated channel 'chatter' in neurons of the rat medulla oblongata
NAADP-mediated channel 'chatter' in neurons of the rat medulla oblongata
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DOI：
10.1042/bj20081138
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发表时间：
2009-04-01
影响因子：
4.1
通讯作者：
Dun, Nae J.
中科院分区：
文献类型：
--
作者：
Brailoiu, G. Cristina;Brailoiu, Eugen;Dun, Nae J.
NAADP(烟酸-腺嘌呤二核苷酸磷酸)是一种强大的钙动员信使，能刺激多种细胞中的钙释放。NAADP敏感的Ca~(2+)通道被认为驻留在油酸性的Ca~(2+)库中，并与位于内质网的IP3(1，4，5-三磷酸肌醇)和/或ryanodine受体功能偶联。然而，NAADP敏感的钙通道是否“颤动”到其他通道尚不清楚。在本研究中，我们使用了一种细胞特有的NAADP类似物来探索NAADP在大鼠延髓神经元中的反应。在分离的神经元上，NAADP-AM(NAADP-乙酰氧甲酯)可诱发整体胞浆内钙信号，这种信号可被外部钙离子去除而幅度降低，可被酸性隔室破坏而取消，并可被兰诺定受体阻断而基本上被抑制。在大鼠延髓切片上，NAADP-AM在细胞内EGTA存在的情况下使疑核神经元去极化，但不能在较快的钙离子螯合剂BAPTA[1，2-双(邻氨基苯氧基)乙烷-N，N，N‘，N’-四乙酸]的作用下使疑核神经元去极化。去极化还依赖于细胞外钙离子、酸性储存和兰尼定受体。在电压钳制模式下，NAADP-AM产生内向电流，其反转电位约为。0 mV时，本研究结果显示，延髓神经元中存在酸性的NAADP敏感的钙离子储存库，其动员不仅导致全局的钙离子信号，而且还导致局部信号，激活细胞表面的非选择性阳离子通道，从而导致去极化。因此，NAADP能够协调细胞内部和细胞膜上的通道，代表了一种新的中枢神经元兴奋机制。
NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca2+-mobilizing messenger that stimulates Ca2+ release in a variety of cells. NAADP-sensitive Ca2+ channels are thought to reside oil Acidic Ca2+ stores and to he functionally coupled to IP3 (inositol 1,4,5-trisphosphate) and/or ryanodine receptors located oil the endoplasmic reticulum. Whether NAADP-sensitive Ca2+ channels 'chatter' to other channels, however, is not clear. In the present Study, we have used a cell-permeant NAADP analogue to probe NAADP-mediated responses in rat medulla oblongata neurons. NAADP-AM (NAADP-acetoxymethyl ester) evoked global cytosolic Ca2+ signals in isolated neurons that were reduced in amplitude by removal of external Ca2+, abolished by disruption of acidic compartments and substantially inhibited by blockade of ryanodine receptors. In rat medullary slices, NAADP-AM depolarized neurons from the nucleus ambiguus in the presence of intracellular EGTA, but not of the faster Ca2+ chelator BAPTA [1,2-bis-(o-aminophenox)ethane-N,N,N',N'-tetra-acetic acid]. Depolarization was also dependent upon extracellular Ca2+, acidic stores and ryanodine receptors. In voltage-clamp mode, NAADP-AM induced an inward Current with a reversal potential of approx. 0 mV, The results of the present study reveal the presence of acidic NAADP-sensitive Ca2+ stores in medulla neurons, the mobilization of which results not only in global Ca2+ signals but also in local signals that activate non-selective cation channels oil the cell surface resulting in depolarization. Thus NAADP is capable of co-ordinating channels both within the cell interior and at the cell membrane representing a novel mechanism for excitation of central neurons.