DEVELOPMENTAL EXPRESSION OF CLC-2 IN THE RAT NERVOUS-SYSTEM

Regulation of expression of the voltage-gated chloride channel, ClC-2, was investigated during development and adult life in rat brain. RNas e protection assays demonstrated a marked increase in levels of expres sion of ClC-2 in brain during early postnatal development which was al so detected in adult brain. In situ hybridization of E15 and E18 rat b rains demonstrated ClC-2 expression in deep brain nuclei and scattered cells within the neuroepithelial layers, but not in the regions of su bventricular zone that primarily give rise to glial populations. By El s all neurons within the emerging cortical plate and its equivalent in other areas of the CNS were heavily labeled. During the first postnat al week, ClC-2 was highly expressed in most neurons. By P7 a pattern o f differential expression emerged with evidence of decreased expressio n of ClC-2 mRNA in many neuronal populations. In adult rat brain, ClC- 2 was expressed at highest levels in large neurons as found within lay er V of cortex, Ammon's Horn of hippocampus, or mitral cells of the ol factory bulb and Purkinje cells within the cerebellum. Many smaller ne urons within the diencephalon maintained significant levels of express ion. A functional conductance was readily detected in hippocampal neur ons during the first postnatal week, which had the same characteristic properties as the conductance observed in adult neurons. The observed expression and functional presence of ClC-2 suggest a widespread role in neuronal chloride homeostasis in early postnatal life, and demonst rated that cell specific shut-down resulted in the adult pattern of ex pression. (C) 1998 Elsevier Science B.V. All rights reserved.