Low expression of the CIC-2 chloride channel during postnatal development:a mechanism for the paradoxical depolarizing action of GABA and glycine inthe hippocampus
M. Mladinic et al., Low expression of the CIC-2 chloride channel during postnatal development:a mechanism for the paradoxical depolarizing action of GABA and glycine inthe hippocampus, P ROY SOC B, 266(1425), 1999, pp. 1207-1213
Citations number
27
Categorie Soggetti
Experimental Biology
Journal title
PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
In early postnatal development, during the period of synapse formation, gam
ma-aminobutyric acid (GABA) and glycine, the main inhibitory transmitters i
n the adult brain! paradoxically excite and depolarize neuronal membranes b
y an outward flux of chloride. The mechanisms of chloride homeostasis are n
ot fully understood. It is known chat in adult neurons intracellular chlori
de accumulation is prevented by a particular type of chloride channel, the
ClC-2. This channel strongly rectifies in the inward direction at potential
s negative to E-Cl thus ensuring chloride efflux. We have tested the hypoth
esis that in the developing hippocampus, a differential expression or regul
ation of ClC-2 channels may contribute to the depolarizing action of GABA a
nd glycine. We have cloned a truncated form of ClC-2 (ClC-2nh) from the neo
natal hippocampus which lacks the 157 bp corresponding to exon 2. In situ h
ybridization experiments show that ClC-2nh is the predominant form of ClC-2
mRNA in the neonatal brain. ClC-2nh mRNA is unable to encode a full-length
protein due to a frameshift, consequently it does not induce any currents
upon injection into Xenopus oocytes. Low expression of the full-length ClC-
2 channel, could alter chloride homeostasis, lead to accumulation of [Cl-](
i) and thereby contribute to the depolarizing action of GABA and glycine du
ring early development.