Miniature synaptic events elicited by presynaptic Ca2+ rise are selectively suppressed by cannabinoid receptor activation in cerebellar Purkinje cells
Miniature synaptic events elicited by presynaptic Ca2+ rise are selectively suppressed by cannabinoid receptor activation in cerebellar Purkinje cells
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DOI：
10.1523/jneurosci.2258-05.2006
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发表时间：
2006-01-04
影响因子：
5.3
通讯作者：
Kano, M
中科院分区：
文献类型：
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作者：
Yamasaki, M;Hashimoto, K;Kano, M
大麻素受体的激活抑制了不同脑区的神经递质释放。在小脑浦肯野细胞（PC），大麻素激动剂抑制EPSC和IPSC通过刺激相应的输入诱发。然而，大麻素激动剂在正常外部Ca 2+浓度（[Ca 2 +]（o））下抑制微型IPSC（mIPSC），但不抑制微型EPSC（mEPSC）。因此，大麻素激动剂被认为抑制IPSC的释放机制，但不抑制EPSC的释放机制。在这里，我们调查了这种差异的可能原因，发现大麻素激动剂选择性抑制Ca 2+增强的微型事件。大麻素激动剂，WIN 55，212-2（5 μ M），不影响mEPSC频率与2 mM细胞外Ca 2+（Ca 2+（o））。然而，当通过用5 mMCa（o）（2+）灌注或浴用Ca 2+载体A23187升高突触前Ca 2+水平来增强mEPSC频率时，WIN 55，212-2变得有效。相反，WIN 55，212-2用2 mM Ca-o（2+）抑制mIPSC频率，但当用含有BAPTA-AM的无Ca 2+溶液灌注降低突触前Ca 2+水平时，它变得无效。系统性[Ca ~（2+）]（o）变化的实验表明，mIPSC而不是mEPSC有规律地涉及由突触前Ca ~（2+）升高引起的事件，2 mM Ca ~（2+）。更重要的是，mEPSC和mIPSC的Ca 2+增强并不归因于电压依赖性Ca 2+通道的激活。激活GABA（B）受体或与G（i/o）蛋白偶联的III组代谢型谷氨酸受体也优先抑制PC中Ca 2+增强的微事件。这些结果表明，在正常[Ca 2 +]（o）时，Ca 2+增强的微型事件的发生决定了PC对大麻素受体和其他G（i/o）偶联受体介导的突触前抑制的敏感性。
Activation of cannabinoid receptors suppresses neurotransmitter release in various brain regions. In cerebellar Purkinje cells (PCs), cannabinoid agonists suppress both EPSC and IPSC evoked by stimulating the corresponding inputs. However, cannabinoid agonists suppress miniature IPSC (mIPSC) but not miniature EPSC (mEPSC) at normal external Ca2+ concentration ([Ca2+](o)). Therefore, cannabinoid agonists are thought to suppress release machinery for IPSCs but not that for EPSCs. Here we investigated the possible cause of this difference and found that cannabinoid agonists selectively suppressed Ca2+-enhanced miniature events. A cannabinoid agonist, WIN55,212-2 (5 mu M), did not affect mEPSC frequency with 2 mM extracellular Ca2+ (Ca2+(o)). However, WIN55,212-2 became effective when mEPSC frequency was enhanced by elevation of presynaptic Ca2+ level by perfusion with 5mMCa(o)(2+) or bath application of A23187, a Ca2+ ionophore. In contrast, WIN55,212-2 suppressed mIPSC frequency with 2mM Ca-o(2+), but it became ineffective when the presynaptic Ca2+ level was lowered by perfusion with a Ca2+-free solution containing BAPTA-AM. Experiments with systematic [Ca2+](o) changes revealed that mIPSC but not mEPSC regularly involved events elicited by presynaptic Ca2+ rise with 2mM Ca-o(2+). Importantly, Ca2+-enhancement of mEPSC and mIPSC was not attributable to activation of voltage-dependent Ca2+ channels. Activation of GABA(B) receptor or group III metabotropic glutamate receptor, which couple to G(i/o)-protein, also preferentially suppressed Ca2+-enhanced miniature events in PCs. These results suggest that the occurrence of Ca2+-enhanced miniature events at normal [Ca2+](o) determines the sensitivity to the presynaptic depression mediated by cannabinoid receptors and other G(i/o)-coupled receptors in PCs.