Functional coupling between ryanodine receptors and L-type calcium channels in neurons
Functional coupling between ryanodine receptors and L-type calcium channels in neurons
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DOI：
10.1038/382719a0
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发表时间：
1996-08-22
期刊：
影响因子：
64.8
通讯作者：
Bockaert, J
中科院分区：
文献类型：
--
作者：
Chavis, P;Fagni, L;Bockaert, J
在骨骼肌中，L型Ca 2+通道作为电压传感器控制肌浆网中的鱼米碱敏感性Ca 2+通道（1）。最近已经证明，这些ryanodine受体产生逆行信号，改变L型Ca 2+通道活性（2）。在这里，我们证明了兰尼碱受体和L型Ca ~（2+）通道在神经元中的紧密功能耦合。在小脑颗粒细胞中，1型代谢型谷氨酸受体（mGluR 1）的激活诱导了L型Ba ~（2+）电流的大幅度振荡增加。激活作用不依赖于肌醇1，4，5-三磷酸和经典蛋白激酶，但可被咖啡因模拟，并被ryanodine阻断。这种阻断的动力学依赖于Ba ~（2+）电流刺激的频率。ryanodine抑制mGluR 1和咖啡因激活的L型Ca 2+通道。这些结果证明了一种新的机制，在神经元中的Ca 2+通道调制。
IN skeletal muscle, L-type Ca2+ channels act as voltage sensors to control ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum(1). It has recently been demonstrated that these ryanodine receptors generate a retrograde signal that modifies L-type Ca2+-channel activity(2). Here we demonstrate a tight functional coupling between ryanodine receptors and L-type Ca2+ channel in neurons, In cerebellar granule cells, activation of the type-1 metabotropic glutamate receptor (mGluR1) induced a large, oscillating increase of the L-type Ba2+ current. Activation occurred independently of inositol 1,4,5-trisphosphate and classical protein kinases, but was mimicked by caffeine and blocked by ryanodine, The kinetics of this blockade were dependent on the frequency of Ba2+ current stimulation, Both mGluR1- and caffeine-induced increase in L-type Ca2+-channel activity persisted in inside-out membrane patches, In these excised patches, ryanodine suppressed both the mGluR1- and caffeine-activated L-type Ca2+ channels. These results demonstrate a novel mechanism for Ca2+-channel modulation in neurons.