中枢神経系における細胞内カルシウムイオンの役割と作用機作に関する一考察

Abstract

When the stimuli by nerve impulses, neurotransmitters, hormones, peptides and growth factors are administered to the neurons, one of the responses of the nerve cells is the enhancement of Ca2+ influx and/or the release of Ca2+ from the intracellular storage site. Ca2+ may be related to several types of neuronal functions such as biosynthesis of neurotransmitters, stimulus-secretion coupling of neurotransmitters and hormones, microtubule assembly-disassembly cycle and many metabolic reactions. Although the precise molecular mechanism mediating the actions of Ca2+ in the brain remains to be elucidated, accumulating evidence suggests that the actions of Ca2+ are mediated through Ca2(+)-binding proteins. The role of troponin C, a Ca2(+)-binding protein, was extensively studied in the skeletal muscle first. Subsequently calmodulin, a ubiquitous Ca2(+)-binding protein, was found to be widely distributed in many tissues and to be involved in a variety of Ca2(+)-mediated cellular processes. In an attempt to elucidate Ca2+ actions in the central nervous system, we have been studying Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and calcineurin (Ca2+/calmodulin-dependent protein phosphatase). These enzymes have many common substrates and, therefore, may be involved in the neuronal functions via phosphorylation and dephosphorylation of specific proteins.