TRPM channels modulate epileptic-like convulsions via systemic ion homeostasis.
TRPM channels modulate epileptic-like convulsions via systemic ion homeostasis.
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DOI：
10.1016/j.cub.2011.03.070
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发表时间：
2011-05-24
期刊：
影响因子：
9.2
通讯作者：
Jin, Yishi
中科院分区：
文献类型：
--
作者：
Stawicki, Tamara M.;Zhou, Keming;Yochem, John;Chen, Lihsia;Jin, Yishi
神经元网络在广泛的活动水平上运作，神经元和非神经元细胞都有助于兴奋和抑制的平衡。神经网络内的活动不平衡是许多神经系统疾病（如癫痫）的基础。秀丽隐杆线虫的运动回路是通过协调胆碱能兴奋传递和gaba能抑制传递来运作的。我们之前已经证明，神经元乙酰胆碱受体acr-2（gf）的功能获得突变会导致类似癫痫的抽搐行为。在这里，我们报道了acr-2（gf）的行为和生理作用需要非神经元组织中TRPM通道GTL-2的活性。gtl-2功能的丧失不影响基线突触传递，但可以补偿acr-2（gf）引起的兴奋-抑制失衡。去除gtl-2的代偿作用被另一个TRPM通道GTL-1抵消，并且可以通过二价阳离子螯合剂（包括针对Zn2+的螯合剂）的急性治疗来重现。综上所述，这些数据揭示了离子稳态在神经元网络活动平衡中的重要作用，以及非神经元TRPM通道在神经网络活动微调中的新功能。
Neuronal networks operate over a wide range of activity levels, with both neuronal and non-neuronal cells contributing to the balance of excitation and inhibition. Activity imbalance within neuronal networks underlies many neurological diseases, such as epilepsy. The C. elegans locomotor circuit operates via coordinated activity of cholinergic excitatory and GABAergic inhibitory transmission. We have previously shown that a gain-of-function mutation in a neuronal acetylcholine receptor, acr-2(gf), causes an epileptic-like convulsion behavior. Here, we report that the behavioral and physiological effects of acr-2(gf) require the activity of the TRPM channel GTL-2 in non-neuronal tissues. Loss of gtl-2 function does not affect baseline synaptic transmission, yet can compensate for the excitation-inhibition imbalance caused by acr-2(gf). The compensatory effects of removing gtl-2 are counter-balanced by another TRPM channel GTL-1, and can be recapitulated by acute treatment with divalent cation chelators, including those specific for Zn2+. Together these data reveal an important role for ion homeostasis in the balance of neuronal network activity and a novel function of non-neuronal TRPM channels in the fine-tuning of this network activity.
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