神経細胞内クロライドイオン濃度の制御系とその人工修飾 : クロライドイオンとシグナルトランスダクション

概要

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Intracellular chloride ion concentration ([Cl-]i) plays an important role in cellular functions including the control of membrane potential and excitability. In neurons, Cl equilibrium potential (ECl) is lower or higher than the membrane potential (Em), suggesting that [Cl-]i is lower or higher than that expected from passive distribution. As the mechanisms to control [Cl-]i, active outwardly or inwardly directed Cl- transport systems have been reported. The former includes Na+-dependent Cl-/HCO3- exchanger, K+/Cl- cotransporter and ATP-dependent Cl- pump; and the latter includes Na+/K+/2Cl- cotransporter and amino acid-dependent Na+/Cl cotransporter. In hippocampal pyramidal cells, recent studies using a Cl--sensitive fluorescent probe to monitor [Cl-]i revealed the presence of an ATPdependent Cl- pump and a Na+/K+/2Cl- contransporter, and an uneven distribution of [Cl-]i (cell body<dendrite) and these Cl- transport systems. Intracerebroventricular administration of an inhibitor of the ATP-dependent Cl- pump, ethacrynic acid, induces status epilepticus in mice. Thus, it appears to be necessary to elucidate cellular and molecular mechanisms of Cl- transporters and their control systems for a better understanding of Cl--related functions in neurons.
社団法人日本薬理学会の論文