抄録
Focal cortical dysplasia is one of the important causes of intractable epilepsies and characterized histologically by disorganized cortical lamination and cytomegalic dysplastic neurons. GABA is a major inhibitory transmitter in the brain. However, in immature neurons, GABA has an excitatory action because of a high intracellular Cl− concentration. The change in GABAergic functions regulated by an alteration in Cl− homeostasis, plays an important role in neocortical development by modulating such events as laminar organization and synaptogenesis. Cation-Cl− cotransporters play a critical role in the regulation of [Cl−]i, and of these NKCC1 promotes accumulation of Cl− into, whereas KCC2 extrudes it out of the cell. Functional alterations in Cl− homeostasis are known to be induced by neuronal insults such as trauma or axotomy. To investigate alterations in Cl− homeostasis in human cortical dysplasia, NKCC1 and KCC2 expressions were examined by in situ hybridization histochemistry and immunohistochemistry. KCC2 mRNA and protein are expressed in both normal and displasic neurons. KCC2 mRNA and protein expressions were downregulated in the neurons around dysplastic neurons. NKCC1 expression was not changed. These results suggested that decrease of KCC2 expression might be changed GABAergic response to excitatory and be involved in the pathogenesis of dysplastic cortex. [Jpn J Physiol 54 Suppl:S145 (2004)]
