抄録
We previously showed that cultured cortical neurons possess the volume-sensitive Cl− channel which serves as a Cl− efflux pathway for the regulatory volume decrease after hypotonic swelling. It has been reported that neurons show swelling coupled to Na+ influx via NMDA receptors under excitotoxic conditions. In this study we investigated whether an excitotoxic insult activates volume-sensitive Cl− channels in mouse cortical neurons. Exposure to a glutamate receptor agonist, NMDA, activated whole-cell currents that exhibited anion selectivity, outward rectification, inactivation kinetics at large positive potentials and sensitivity to a Cl− channel blocker, NPPB. NMDA-activated anion currents were suppressed by osmotic shrinkage induced by hypertonic solution or by removal of extracellular Na+. Morphological observations in calcein-loaded neurons showed that not only somatic swelling but also varicosity formation on the dendrites were induced by exposure to NMDA. After washout of NMDA, varicosities were found to gradually disappear. Such recovery from dendritic beading was not observed in the presence of NPPB. Taken together, it is suggested that the volume-sensitive outwardly rectifying Cl− channel plays a role in recovery from excitotoxic varicosity formation in cortical neurons. [Jpn J Physiol 54 Suppl:S131 (2004)]
