Nichols R A, Sihra T S, Czernik A J, Nairn A C, Greengard P
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021.
Nature. 1990 Feb 15;343(6259):647-51. doi: 10.1038/343647a0.
A variety of evidence indicates that calcium-dependent protein phosphorylation modulates the release of neurotransmitter from nerve terminals. For instance, the injection of rat calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-dependent PK II) into the preterminal digit of the squid giant synapse leads to an increase in the release of a so-far unidentified neurotransmitter induced by presynaptic depolarization. But until now, it has not been demonstrated that Ca2+/CaM-dependent PK II can also regulate neurotransmitter release in the vertebrate nervous system. Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline. We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release. These results support the hypothesis that activation of Ca2+/CaM-dependent PK II in the nerve terminal removes a constraint on neurotransmitter release.
多种证据表明，钙依赖性蛋白磷酸化调节神经递质从神经末梢的释放。例如，将大鼠钙/钙调蛋白依赖性蛋白激酶II（Ca2+/CaM依赖性PK II）注射到鱿鱼巨大突触的终末前指中，会导致由突触前去极化诱导的一种迄今未鉴定的神经递质释放增加。但直到现在，尚未证明Ca2+/CaM依赖性PK II也能调节脊椎动物神经系统中的神经递质释放。在此我们报告，通过硫代磷酸化自动激活的Ca2+/CaM依赖性PK II引入大鼠脑突触体（分离的神经末梢）会增加两种神经递质（谷氨酸和去甲肾上腺素）诱导释放的初始速率。我们还表明，引入Ca2+/CaM依赖性PK II的选择性肽能抑制剂会抑制诱导的谷氨酸释放的初始速率。这些结果支持了这样一种假设，即神经末梢中Ca2+/CaM依赖性PK II的激活消除了对神经递质释放的限制。
