MEMBRANE DEPOLARIZATION EVOKES NEUROTRANSMITTER RELEASE IN THE ABSENCE OF CALCIUM ENTRY
MEMBRANE DEPOLARIZATION EVOKES NEUROTRANSMITTER RELEASE IN THE ABSENCE OF CALCIUM ENTRY
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DOI：
10.1038/342433a0
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发表时间：
1989-11-23
期刊：
影响因子：
64.8
通讯作者：
PARNAS, I
中科院分区：
文献类型：
--
作者：
HOCHNER, B;PARNAS, H;PARNAS, I
发现Ca 2+是神经递质释放所必需的，神经递质是神经细胞进行通讯的主要手段，这一发现导致了神经递质释放的钙假说1 -4，其中释放在动作电位后仅通过释放部位附近细胞内Ca 2+浓度的增加而启动，并通过Ca 2+的快速去除而终止（1-2 ms）。从那时起，钙电压假说被提出5，6，其中突触前末梢的去极化有两个功能。首先，与钙假说一样，Ca 2+电导增加，从而允许Ca 2+进入。其次，在膜分子中诱导构象变化，使其对Ca 2+敏感，然后Ca 2+与这种活性形式结合触发神经递质的释放。当膜被复极化时，分子被灭活并且释放终止，而不管此时的局部Ca 2+浓度如何。与钙假说相反，该假说解释了释放时间过程对细胞内Ca 2+浓度实验操作的不敏感性7 -11。此外，它解释了去极化后释放的快速终止，即使Ca 2+浓度可能仍然很高。在这里，我们描述了区分这两种假设的实验，发现我们的结果支持钙电压假说。
THE discovery that Ca2+is necessary for the release of neurotransmitter, the primary means by which nerve cells communicate, led to the calcium hypothesis of neutransmitter release1–4, in which release is initiated after an action potential only by an increase in intracellular Ca2+concentration near the release sites and is terminated (1–2 ms) by the rapid removal of Ca2+. Since then, the calcium-voltage hypothesis has been proposed5,6, in which the depolarization of the presynaptic terminals has two functions. First, in common with the calcium hypothesis, the Ca2+conductance is increased, thereby permitting Ca2+entry. Second, a confor-mational change is induced in a membrane molecule that renders it sensitive to Ca2+, and then binding of Ca2+to this active form triggers release of neurotransmitter. When the membrane is repolarized, the molecule is inactivated and release is terminated, regardless of the local Ca2+concentration at that moment. This hypothesis, in contrast to the calcium hypothesis, accounts for the insensitivity of the time course of release to experimental manipulations of intracellular Ca2+concentation7–11, Furthermore, it explains rapid termination of release after depolarization, even though Ca2+concentration may still be high. Here we describe experiments that distinguish between these two hypotheses and find that our results support the calcium voltage hypothesis.