Abstract
It is known that the role of GABAA-R mediated actions is important for early CNS development. The GABAA-R mediate actions can regulate radial migration of cortical plate (CP) cells. GABA content is decreased in the brain of GAD67-GFP knock-in mouse. Therefore, these mice are useful to examine the effects of ambient GABA on CP cells. Since taurine, a partial agonist of GABAA-R, is the most abundant free amino acid in developing brain, the roles of ambient taurine and GABA in activation of GABAA -Rs on CP cells were investigated using GAD67-GFP knock-in mice. The CP cells were labeled by electroporation of mRFP gene. There was no significant difference in the distribution of labeled cells among genotypes of GAD67-GFP knock-in mice. GABAA-R mediated currents were then recorded. Dose-response relationships of evoked GABA current had no differences among genotypes. Ambient taurine was decreased by the i.p. injections of taurine metabolism blocker, D-cysteine sulfinate (D-CSA). The radial migration of CP cells was facilitated in D-CSA injected homozygous GAD67-GFP knock-in mice, in which ambient taurine could give rise to GABAA-R-mediated tonic currents. Chronic application of GABAA-R blocker to homozygous fetal ventricle also facilitated the radial migration of CP cells. These result indicated that taurine may be endogeneous co-agonist for GABAA-R that could play critical role in neocortical development. [J Physiol Sci. 2008;58 Suppl:S83]
