The effects of raising intracellular calcium on synaptic GABA(A) receptor-channels
The effects of raising intracellular calcium on synaptic GABA(A) receptor-channels
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DOI：
10.1016/s0028-3908(96)00063-9
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发表时间：
1996-01-01
影响因子：
4.7
通讯作者：
Mody, I
中科院分区：
文献类型：
--
作者：
De Koninck, Y;Mody, I
用全细胞膜片电极研究了不同钙负荷对齿状回颗粒细胞突触GABA（A）受体通道的影响。自发抑制性突触后电流（sIPSC）的动力学是相似的记录时，没有任何外源性Ca 2+缓冲液中的贴片电极或与高达30 mM的BAPTA在移液管。贴片移液管中20-100 μ M的未缓冲Ca 2+浓度在记录过程中（10-40 min）诱导微型IPSC（mIPSC）衰减的逐渐延长，其上升时间、峰值振幅或发生频率无明显变化。其他二价阳离子如锶不能模拟这种效应。在移液管中用各种亲和螯合剂缓冲的游离离子Ca 2+浓度输注到细胞中对突触GABA（A）电流具有更显著的影响。用BAPTA缓冲在200-400 nM范围内的游离离子Ca 2+延长了mIPSC的衰减时间常数。用相对低亲和力的缓冲液如Br（2）BAPTA将超过1 μ M的缓冲Ca 2+引入神经元中，导致mIPSC的显著抑制。一个类似的效果，观察后释放的Ca 2+从细胞内的商店诱导的咖啡因（10 mM）。我们的结论是，Ca ~（2+）对突触GABA（A）受体通道具有双相作用。与通道爆发持续时间延长一致的高亲和力增强和通道活性的低亲和力抑制均有助于[Ca 2 +]（i）对突触GABA（A）受体的复杂调节，这对神经元兴奋性的可塑性和病理改变的细胞机制具有深远的影响。版权所有（C）1996 Elsevier Science Ltd.
The effects of various calcium (Ca2+) loads imposed through whole-cell patch electrodes on dentate gyrus granule cells were investigated on synaptic GABA(A) receptor-channels. The kinetics of spontaneous inhibitory postsynaptic currents (sIPSCs) were similar when recorded without any exogenous Ca2+ buffers in the patch electrode or with up to 30 mM BAPTA in the pipette. Unbuffered Ca2+ concentrations of 20-100 mu M in the patch pipettes induced a gradual prolongation of miniature IPSC (mIPSC) decays over the course of the recording (10-40 min) with no apparent change in their rise times, peak amplitudes, or frequency of occurrence. This effect was not mimicked by other divalent cations such as strontium. Infusion into the cells of free ionic Ca2+ concentrations buffered with various affinity chelators in the pipette had more pronounced effects on synaptic GABA(A) currents. Free ionic Ca2+ buffered in the range of 200-400 nM with BAPTA prolonged the decay time constant of mIPSCs. Introducing buffered Ca2+ into the neurons in excess of 1 mu M, with a relatively low affinity buffer such as Br(2)BAPTA, resulted in a marked inhibition of mIPSCs. A similar effect was observed following release of Ca2+ from intracellular stores induced by caffeine (10 mM). We conclude that Ca2+ has a biphasic effect on synaptic GABA(A) receptor-channels. A high affinity potentiation, consistent with a prolongation of channel burst duration, and a low affinity depression of channel activity both contribute to a complex regulation of synaptic GABA(A) receptors by [Ca2+](i) that has a profound bearing on cellular mechanisms of plasticity and pathological alterations in neuronal excitability. Copyright (C) 1996 Elsevier Science Ltd.