Calcium homeostasis in trigeminal ganglion cell bodies
Calcium homeostasis in trigeminal ganglion cell bodies
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DOI：
10.1016/j.ceca.2006.08.014
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发表时间：
2007-04-01
期刊：
影响因子：
4
通讯作者：
Weinreich, Daniel
中科院分区：
文献类型：
--
作者：
Gover, Tony D.;Moreira, Thais H. V.;Weinreich, Daniel
在初级感觉传入神经元中，钙离子在受体和突触可塑性、神经递质和营养因子的释放以及基因调控等细胞过程中起着重要的调节作用。目前对初级感觉神经元钙稳态机制的认识主要来源于对背根神经节和结状神经节神经元胞体的研究。三叉神经节神经元(TGNs)内钙稳态的研究较少。为了确定是什么细胞过程对TGNs中电诱导的钙瞬变做出贡献，我们用一组药理试剂探索了TGN细胞体中从眼部分裂的钙调节机制。在Fura-2负载的TGNs中，用短时间(500ms)的50 mM KCl去极化TGNs可诱发出钙瞬变。肌浆网/内质网钙-三磷酸腺苷酶(SERCA)的抑制剂环匹亚硝酸(CPA；5 mU M)可显著降低KCl2诱发的TGNs钙瞬变的峰值，并延缓其衰变。线粒体原载体--3-氯苯肼(CCCP；5 mU M)显著增加KCl2+诱导的钙瞬变的峰值。这些数据表明，在TGN细胞体中，钙离子储存确实在钙稳态中起着重要作用。为了确定钠钙交换器(NCX)在KCl2诱导的TGNs钙瞬变中的作用，我们用KB-R7943(10mU M)或用Li+替代Na+来抑制该交换器。对NCX的抑制既不影响KCl诱发的钙瞬变的峰值幅度，也不影响其衰减动力学。因此，NCX在清除TGNs胞浆钙离子方面不起重要作用。为了测试质膜钙-ATPase(PMCA)是否有助于钙离子的排出，我们通过改变碱性pH(9.0)来抑制其活性。在pH为9.0时，KCl2诱导的钙瞬变的峰值和衰减时间均显著增加。这些数据表明，在TGNs中，PMCA是电活动后清除胞内钙的主要机制。(C)2006爱思唯尔有限公司。保留所有权利。
In primary sensory afferent neurons, Ca2+ plays a vital role in the regulation of cellular processes including receptor and synaptic plasticity, neurotransmitter and trophic factor release and gene regulation. Current understanding of the mechanisms underlying Ca2+ homeostasis of primary sensory afferent neurons is mostly derived from studies on dorsal root ganglia and nodose ganglia neuron cell bodies. Little is known about Ca2+ homeostasis in trigeminal ganglion neurons (TGNs). To determine what cellular processes contribute to electrically-evoked Ca2+, transients in TGNs, we probed Ca2+ regulatory mechanisms in TGN cell bodies from the ophthalmic division with a panel of pharmacological reagents. Ca2+ transients were evoked in fura-2 loaded TGNs by depolarizing the plasma membrane with brief (500 ms) puffs of 50 MM KCl. Cyclopiazonic acid (CPA; 5 mu M), an inhibitor of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), significantly decreased the peak amplitude, and slowed the decay, of the KCl-evoked Ca2+, transients in TGNs. The mitochondrial protonophore, carbonyl cyanide 3-chloro-phenylhydrazone (CCCP; 5 mu M) significantly increased the peak amplitude of KCl-evoked Ca2+ transients. These data demonstrate that Ca2+ stores do play a major role in Ca2+ homeostasis in TGN cell bodies. To determine the role of the sodium-calcium exchanger (NCX) in KCl-evoked Ca2+ transients in TGNs, we inhibited the exchanger with KB-R7943 (10 mu M), or by replacing Na+ with Li+. NCX inhibition did not affect either the peak amplitude or the decay kinetics of the KCl-evoked Ca2+ transients. Therefore, the NCX does not play a significant role in removing cytosolic Ca2+ from TGNs. To test whether the plasma membrane calcium-ATPase (PMCA) contributes to Ca2+ extrusion, we inhibited its activity by a shift to alkaline pH (9.0). At pH 9.0, both the peak amplitude and decay time of the KCl-evoked Ca2+ transient were increased significantly. These data suggest that, in TGNs, the PMCA is the major mechanism for removing cytosolic Ca2+ following electrical activity. (c) 2006 Elsevier Ltd. All rights reserved.