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

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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.