Naslov
Low expression of the ClC-2 chloride channel during postnatal development : a mechanism for the paradoxical depolarizing action of GABA and glycine in the hippocampus.

Autori
Mladinić Pejatović, Miranda ; Becchetti, Andrea ; Didelon, Frederic ; Bradbury, Andrew ; Cherubini, Enrico

Izvornik
Proceedings of the royal society of london series b-biological sciences (0962-8452) 266 (1999), 1425; 1207-1213

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
chloride channel; alternative splicing; tissue distribution; GABAA receptors; glycine; neonatal brain

Sažetak
In early postnatal development, during the period of synapse formation, gamma-aminobutyric acid (GABA) and glycine, the main inhibitory transmitters in the adult brain, paradoxically excite and depolarize neuronal membranes by an outward flux of chloride. The mechanisms of chloride homeostasis are not fully understood. It is known that in adult neurons intracellular chloride accumulation is prevented by a particular type of chloride channel, the ClC-2. This channel strongly rectifies in the inward direction at potentials negative to ECl thus ensuring chloride efflux. We have tested the hypothesis that in the developing hippocampus, a differential expression or regulation of ClC- 2 channels may contribute to the depolarizing action of GABA and glycine. We have cloned a truncated form of ClC-2 (ClC-2nh) from the neonatal hippocampus which lacks the 157 bp corresponding to exon 2. In situ hybridization 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 during early development.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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