NEUROTRANSMITTER INHIBITION OF NEURONAL CALCIUM CURRENTS BY CHANGES IN CHANNEL VOLTAGE DEPENDENCE
NEUROTRANSMITTER INHIBITION OF NEURONAL CALCIUM CURRENTS BY CHANGES IN CHANNEL VOLTAGE DEPENDENCE
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DOI：
10.1038/340153a0
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发表时间：
1989-07-13
期刊：
影响因子：
64.8
通讯作者：
BEAN, BP
中科院分区：
文献类型：
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作者：
BEAN, BP
许多神经元的电压依赖性钙电流被去甲肾上腺素1-3、GABA4-6 和κ-阿片激动剂7-12 等递质抑制。这种调节可能构成突触前抑制的主要机制1,8,12。尽管最近的研究表明 GTP 结合蛋白参与了电流抑制机制13-19，但这些蛋白的激活如何改变通道的运作仍不清楚。在对这一现象的最初描述中，邓拉普和费施巴赫提出，去甲肾上腺素通过某种方式减少细胞中功能钙通道的数量来发挥作用。与这个假设相反，我发现 Ca2+ 电流的抑制主要是由于发射器引起的通道打开的电压依赖性变化。发射器极大地改变了通道激活的电压依赖性，但由非常大的去极化激活的功能通道的数量几乎没有变化或没有变化。对失活的电压依赖性影响也很小。
THE voltage-dependent calcium current of many neurons is depressed by transmitters such as noradrenaline1-3, GABA4-6, and kappa-opiate agonists7-12. This modulation probably constitutes a major mechanism of presynaptic inhibition1,8,12. Although recent work has implicated GTP-binding proteins in the mechanism of current inhibition13-19, it is still unknown how the activation of those proteins alters the operation of the channels. In their initial description of the phenomenon1, Dunlap and Fischbach proposed that noradrenaline acts by somehow reducing the number of functions calcium channels in the cell. By contrast with this hypothesis, I have found that inhibition of Ca2+current is primarily due to a transmitter-induced change in the voltage-dependence with which channels are opened. Transmitters profoundly alter the voltage-dependence of channel activation, but there is little or no change in the number of functional channels activated by very large depolarizations. There is also little effect on the voltage-dependence of inactivation.