Molecular and Cellular Biological Study on the Actions of Intracellular Calcium Ion in Cultured Cells

神经冲动、各种神经递质和生长激素通过提高细胞内钙离子浓度（Ca^<2+>）发挥作用。Ca^<2+>参与多种神经元功能，包括神经递质的生物合成、神经递质与激素的刺激-分泌耦合、微管组装-拆卸循环、突触可塑性、基因表达和许多代谢反应。这些包括相对于时间进程的短期和长期事件。虽然Ca^<2+>在脑内作用的精确分子机制多种多样，但越来越多的证据表明，Ca^<2+>的作用是通过Ca^<2+>结合蛋白介导的。此外，许多功能最终是由蛋白激酶和蛋白磷酸酶以Ca^<2+>依赖的方式完成的。为了阐明钙信号通路在中枢神经系统中的功能，我们研究了Ca^<2+>/钙调素依赖性蛋白激酶II （CaM kinase II）在神经元、胶质细胞和已建立的细胞系统的原代培养中的激活动态。我们发现，在细胞外刺激下，CaM激酶II通过细胞内Ca^<2+>的升高而被激活。此外，伴随着酶的激活，内源性底物的磷酸化，酶的激活和长期增强被观察到。

Nerve impulses, various neurotransmitters, and growth hormones exert their effects through elevation of the intracellular concentration of calcium ion (Ca^<2+>). Ca^<2+> is involved in several types of neuronal functions including biosynthesis of neurotransmitters, stimulus-secretion coupling of neurotransmitters and hormones, microtubule assembly-diassembly cycle, synaptic plasticity, gene expression and many metabolic reactions. These include the short-term and long-term events with respect to time course. Although the precise molecular mechanisms mediating the actions of Ca^<2+> in the brain diverse, accumulating evidence suggests the effects of Ca^<2+> are mediated through Ca^<2+>-binding proteins. Furthermore, many of the functions are ultimately conducted by protein kinases and protein phosphatases in a Ca^<2+>-dependent manner. In an attempt to elucidate the functions in the central nervous system through calcium signaling pathways, we have been examining the dynamic state of activation of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) in primary cultures of neurons and glias and established cell systems. We found that CaM kinase II is activated through elevation of intracellular Ca^<2+> in response to the extracellular stimuli. Firthermore, with concomitant activation of the enzyme, phosphorylation of endogenous substrates, activation of the enzyme and long-term potentiation were observed.