Elementary events underlying voltage-dependent G-protein inhibition of N-type calcium channels

Elementary events underlying voltage-dependent G-protein inhibition of N-type calcium channels
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DOI:
10.1016/s0006-3495(96)79444-4
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发表时间:
1996-11-01
影响因子:
3.4
通讯作者:
Yue, DT
Yue, DT
中科院分区:
生物学3区
文献类型:
--
作者:
Patil, PG;deLeon, M;Yue, DT

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电压依赖性G蛋白抑制N型钙通道可减少突触前钙内流,急剧减弱神经递质的释放。神经元研究表明G蛋白对N型钙通道具有多种调节作用,所观察到的变化可能反映了G蛋白作用的真正复杂性和/或神经元中多种通道和受体的复杂相互作用。重组M2-毒蕈碱受体和N型通道在HEK 293细胞中的表达允许在隔离中研究电压依赖性抑制。在这个系统中,受体激活的G蛋白只有一个作用:在膜去极化后,通道首次打开所需的时间增加了10倍。通道首次打开后,门控没有变化,调制也没有明显改变单位电流。尽管它的简单性,这个单一的变化成功地解释了复杂的变化,在G蛋白抑制神经元的过程中观察到的全细胞电流。
Voltage-dependent G-protein inhibition of N-type calcium channels reduces presynaptic calcium entry, sharply attenuating neurotransmitter release, Studies in neurons demonstrate that G-proteins have multiple modulatory effects on N-type channels, The observed changes may reflect genuine complexity in G-protein action and/or the intricate interactions of multiple channels and receptors in neurons. Expression of recombinant M2-muscarinic receptors and N-type channels in HEK 293 cells allowed voltage-dependent inhibition to be studied in isolation. In this system, receptor-activated G-proteins had only one effect: a 10-fold increase in the time required for channels to first open following membrane depolarization. There were no changes in gating after the channel first opened, and unitary currents were not detectably altered by modulation. Despite its simplicity, this single change successfully accounts for the complex alterations in whole-cell current observed during G-protein inhibition in neurons.