BELL-SHAPED CALCIUM-RESPONSE CURVES OF INS(1,4,5)P3-GATED AND CALCIUM-GATED CHANNELS FROM ENDOPLASMIC-RETICULUM OF CEREBELLUM
BELL-SHAPED CALCIUM-RESPONSE CURVES OF INS(1,4,5)P3-GATED AND CALCIUM-GATED CHANNELS FROM ENDOPLASMIC-RETICULUM OF CEREBELLUM
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DOI：
10.1038/351751a0
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发表时间：
1991-06-27
期刊：
影响因子：
64.8
通讯作者：
EHRLICH, BE
中科院分区：
文献类型：
--
作者：
BEZPROZVANNY, I;WATRAS, J;EHRLICH, BE
细胞内钙的释放有两条途径，一条是1，4，5-三磷酸肌醇(InsP3)门控通道1-3，另一条是钙门控通道(兰尼定受体)4-6。利用特异性抗体，在小脑7，8的浦肯野细胞中发现了这两种受体。我们现在通过将犬小脑的内质网囊泡掺入平面双层，比较了与这两种受体对应的通道的功能特性。InsP3门控通道是最常见的通道。另一种通道类型被腺嘌呤核苷酸或咖啡因激活，被Ru红抑制，并被Ryanodine修饰，这是Ryanodine受体/通道6的特征。两种类型通道的开放概率都呈钟形曲线，依赖于钙。对于InsP3门控通道，最大开放概率出现在0.2mU-M游离钙时，且在最大值两侧急剧下降。Ryanodine受体/通道的最大活动维持在1至100 mU-M钙之间。因此，在胞浆钙的生理范围内，InsP3门控通道本身允许钙释放的正反馈，然后负反馈，而兰尼定受体/通道仅作为钙激活通道发挥作用。同一细胞内存在两个对钙离子反应不同、配体敏感性不同的通道，这为细胞内钙调节的复杂模式提供了基础。
RELEASE of calcium from intracellular stores occurs by two pathways, an inositol 1,4,5-trisphosphate (InsP3)-gated channel 1-3 and a calcium-gated channel (ryanodine receptor) 4-6. Using specific antibodies, both receptors were found in Purkinje cells of cerebellum 7,8. We have now Compared the functional properties of the channels corresponding to the two receptors by incorporating endoplasmic reticulum vesicles from canine cerebellum into planar bilayers. InsP3-gated channels were observed most frequently. Another channel type was activated by adenine nucleotides or caffeine, inhibited by ruthenium red, and modified by ryanodine, characteristics of the ryanodine receptor/channel 6. The open probability of both channel types displayed a bell-shaped curve for dependence on calcium. For the InsP3-gated channel, the maximum probability of opening occurred at 0.2-mu-M free calcium, with sharp decreases on either side of the maximum. Maximum activity for the ryanodine receptor/channel was maintained between 1 and 100-mu-M calcium. Thus, within the physiological range of cytoplasmic calcium, the InsP3-gated channel itself allows positive feedback and then negative feedback for calcium release, whereas the ryanodine receptor/channel behaves solely as a calcium-activated channel. The existence in the same cell of two channels with different responses to calcium and different ligand sensitivities provides a basis for complex patterns of intracellular calcium regulation.