THE INVOLVEMENT OF MULTIPLE CALCIUM-CHANNEL SUBTYPES IN GLUTAMATE RELEASE FROM CEREBELLAR GRANULE CELLS AND ITS MODULATION BY GABA(B) RECEPTOR ACTIVATION
THE INVOLVEMENT OF MULTIPLE CALCIUM-CHANNEL SUBTYPES IN GLUTAMATE RELEASE FROM CEREBELLAR GRANULE CELLS AND ITS MODULATION BY GABA(B) RECEPTOR ACTIVATION
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DOI：
10.1016/0306-4522(95)00172-f
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发表时间：
1995-09-01
期刊：
影响因子：
3.3
通讯作者：
DOLPHIN, AC
中科院分区：
文献类型：
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作者：
HUSTON, E;CULLEN, GP;DOLPHIN, AC
在这项研究中，我们已经研究了各种钙通道亚型的能力，以支持[H-3]谷氨酸从小脑颗粒神经元的释放和GABA（B）受体激动剂，（-）-巴氯芬参与谷氨酸释放的调制的作用机制。通过K+诱发的去极化刺激小脑颗粒神经元释放新合成的[H-3]谷氨酸。刺激释放是完全依赖钙和废除的存在下，200 μ M镉。谷氨酸的释放不受河豚毒素或5-氨基磷酸戊酸的影响，但被二氢红藻氨酸增强，并被6-氰基-7-硝基喹喔啉-2，3-二酮抑制。L-型钙通道阻滞剂尼卡地平和N-型钙通道阻滞剂ω-芋螺毒素GVIA均能部分抑制谷氨酸的释放;但是，在此情况下，P/Q型钙通道阻滞剂omega-芋螺毒素IVA仅在用omega-芋螺毒素GVIA预孵育细胞后才抑制谷氨酸的释放，在Ca ~（2+）或Ba ~（2+）存在下均观察到K ~+刺激的谷氨酸释放并且在两种条件下观察到（-）-巴氯芬对释放的类似抑制。与这些结果相反，离子霉素诱发的谷氨酸释放大大减少相比，K+诱发的释放，并没有调制（-）-巴氯芬。在单独的ω-芋螺毒素GVIA的存在下，（-）-巴氯芬的释放抑制减弱，但没有消除。阻断尼卡地平敏感性通道后，仍然存在（-）-巴氯芬对释放的抑制，并且在预先阻断ω-芋螺毒素GVIA敏感性通道后，尼卡地平的存在恢复了（-）-巴氯芬抑制谷氨酸残留释放的能力。（-）-巴氯芬对谷氨酸释放的调节作用不受单独存在的ω-agatoxin IVA的影响;然而，在阻断ω-芋螺毒素GVIA-和ω-龙舌兰毒素IVA-敏感通道后，这些结果表明，小脑颗粒神经元突触前末梢存在多种类型的电压依赖性钙通道，并支持K+-ATP的释放。刺激释放[H-3]谷氨酸。GABA（B）受体激活对释放的调节似乎依赖于该受体与许多电压敏感性钙通道的相互作用，包括ω-芋螺毒素GVIA敏感性和ω-蛇曲霉毒素IVA敏感性通道。
In this study, we have examined both the ability of various Ca2+ channel sub-types to support the release of [H-3]glutamate from cerebellar granule neurons and the mechanism of action involved in the modulation of glutamate release by the GABA(B) receptor agonist, (-)-baclofen. Cerebellar granule neurons were stimulated to release newly synthesized [H-3]glutamate by K+-evoked depolarization. Stimulated release was entirely calcium-dependent and abolished by the presence of 200 mu M cadmium. Release of glutamate was not affected by either tetrodotoxin or 5-aminophosphonovaleric acid but was potentiated by dihydrokainate and inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione. Stimulated glutamate release was partially inhibited by both the L-type calcium channel blocker, nicardipine, and the N-type calcium channel blocker, omega-conotoxin GVIA; however, the P/Q-type calcium channel blocker omega-agatoxin IVA inhibited release of glutamate only after pre-incubation of cells with omega-conotoxin GVIA.K+-stimulated release of glutamate was observed when stimulated either in the presence of Ca2+ or of Ba2+ and similar inhibition of release by (-)-baclofen was seen under both conditions. In contrast to these results, ionomycin-evoked glutamate release was greatly reduced as compared to K+-evoked release and was not modulated by (-)-baclofen. In the presence of omega-conotoxin GVIA alone, inhibition of release by (-)-baclofen was attenuated but not abolished. Following block of nicardipine-sensitive channels, inhibition of release by (-)-baclofen was still present, and after prior block of omega-conotoxin GVIA-sensitive channels the presence of nicardipine restored the ability of (-)-baclofen to inhibit residual release of glutamate. Modulation of glutamate release by (-)-baclofen was unaffected by the presence of omega-agatoxin IVA alone; however, after block of both omega-conotoxin GVIA- and omega-agatoxin IVA-sensitive channels, inhibition of release by (-)-baclofen was completely abolished.These results indicate that multiple sub-types of voltage-dependent calcium channels are present on the presynaptic terminals of cerebellar granule neurons and support K+-stimulated release of [H-3]glutamate. Modulation of release by GABA(B) receptor activation appears to be dependent upon interaction of this receptor with a number of voltage-sensitive calcium channels, including omega-conotoxin GVIA-sensitive and omega-agatoxin IVA-sensitive channels.