[Neuronal intracellular chloride ion concentrations and their regulatory mechanisms]

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 ATP-dependent Cl- pump and a Na+/K+2Cl- cotransporter, and an uneven distribution of [Cl-]i (cell body less than 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.