Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons
Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons
复制标题
DOI：
10.1046/j.1460-9568.1998.00243.x
复制
发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Fagni, L
中科院分区：
文献类型：
--
作者：
Chavis, P;Ango, F;Fagni, L
由于代谢型谷氨酸受体I型(MGluR1)与小脑颗粒细胞中的RyR，Chavis等人(RyR，Chavis等人，1996年)偶联，我们研究了这种偶联是否能激活培养的小脑颗粒细胞中对钙敏感的K+通道，即大K+(BK)通道。我们观察到(+/-)-1-amino-cyclopentane-trans-1，3-dicarboxylic酸(t-Acpd)和喹乙醇(QA)对BK通道的兴奋作用。而(2S，3S，4S)-α-羧基环丙基甘氨酸(L-CCG-I)和L-(+)-2-氨基-4-膦酸丁酸酯(L-AP4)对BK通道无影响，提示I组mGluRs具有特异性激活作用。I组mGluRs刺激基础BK通道活动被咖啡因模拟，兰尼定和硝苯地平可阻断这两种作用。有趣的是，卡巴胆碱刺激BK通道活动，但通过百日咳毒素敏感的途径，而不是L型钙通道活动。我们的研究表明，与M受体不同的是，I组mGluRs通过动员涉及RyR和L类钙通道的额外途径来激活BK通道。
As metabotropic glutamate receptor type I (mGluR1) is known to couple L-type Ca2+ channels and ryanodine receptors (RyR, Chavis et al., 1996) in cerebellar granule cells, we examined if such a coupling could activate a Ca2+-sensitive K+ channel, the big K+ (BK) channel, in cultured cerebellar granule cells. We observed that (+/-)-1-amino-cyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) and quisqualate (QA) stimulated the activity of BK channels. On the other hand, (2S, 3S, 4S)-alpha-carboxycyclopropyl-glycine (L-CCG-I) and L-(+)-2-amino-4-phosphonobutyrate (L-AP4) had no effect on BK channels, indicating a specific activation by group I mGluRs. Group I mGluRs stimulation of the basal BK channel activity was mimicked by caffeine and both effects were blocked by ryanodine and nifedipine. Interestingly, carbachol stimulated BK channel activity but through a pertussis toxin (PTX)-sensitive pathway that was independent of L-type Ca2+ channel activity. Our report indicates that unlike the muscarinic receptors, group I mGluRs activate BK channels by mobilizing an additional pathway involving RyR and L-type Ca2+ channels.