Calmodulin systems in neuronal excitability: a molecular approach to epilepsy.
Calmodulin systems in neuronal excitability: a molecular approach to epilepsy.
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DOI：
10.1002/ana.410160716
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发表时间：
1984
影响因子：
11.2
通讯作者：
R. Delorenzo
中科院分区：
文献类型：
--
作者：
R. Delorenzo
钙调蛋白是一种主要的 Ca2+ 结合蛋白，可介导神经元功能中的许多 Ca2+ 调节过程。钙调蛋白存在于与突触小泡相关的突触前神经末梢和突触后密度部分中。已经确定了几种钙调蛋白调节的突触生化过程。这些结果表明钙调蛋白可以调节神经元兴奋性的某些方面。苯妥英、卡马西平和苯二氮卓类药物抑制 Ca2+-钙调蛋白调节的蛋白质磷酸化和突触小泡释放的神经递质。已鉴定出苯二氮卓类药物的可饱和立体特异性膜结合位点。苯二氮卓类药物与这些位点结合的效力与其抑制最大电击引起的癫痫发作的能力相关。苯妥英和卡马西平可以取代苯二氮卓类药物从这些结合位点的结合。与这些“抗惊厥”位点的结合可调节完整突触体制剂中 Ca2+ -钙调蛋白刺激的膜蛋白磷酸化和去极化依赖性 Ca2+ 摄取。这些结果提供了主要抗惊厥药物调节突触处的 Ca2+-钙调蛋白系统的证据。 Kindling 改变脑膜中的 Ca2+ -钙调蛋白磷酸化。此外，Ca2+-钙调蛋白激酶系统的改变与一些癫痫易感小鼠品系有关。因此，来自多个来源的证据表明，钙调蛋白介导的过程可能在神经元兴奋性改变和某些形式的癫痫发作的发展中发挥作用。
Calmodulin is a major Ca2+ -binding protein that may mediate many Ca2+ -regulated processes in neuronal function. Calmodulin is present in the presynaptic nerve terminal in association with synaptic vesicles and in postsynaptic density fractions. Several calmodulin-regulated synaptic biochemical processes have been identified. These results indicate that calmodulin may modulate some aspects of neuronal excitability. Phenytoin, carbamazepine, and the benzodiazepines inhibit Ca2+ -calmodulin-regulated protein phosphorylation and neurotransmitter release by synaptic vesicles. A saturable, stereospecific membrane binding site has been identified for the benzodiazepines. The potency of the benzodiazepines to bind to these sites correlates with their ability to inhibit maximal electroshock-induced seizures. Phenytoin and carbamazepine can displace benzodiazepine binding from these binding sites. Binding to these "anticonvulsant" sites regulates Ca2+ -calmodulin-stimulated membrane protein phosphorylation and depolarization-dependent Ca2+ uptake in intact synaptosome preparations. These results provide evidence that major anticonvulsant drugs regulate Ca2+ -calmodulin systems at the synapse. Kindling alters Ca2+ -calmodulin protein phosphorylation in brain membrane. In addition, alterations in Ca2+ -calmodulin kinase systems have been associated with some strains of seizure-susceptible mice. Thus, evidence from multiple sources suggests that calmodulin-mediated processes may play a role in the development of altered neuronal excitability and in some forms of seizure disorders.