Brain regional heterogeneity of pH effects on GABA(A) receptor-associated [35s]TBPS binding.

Abstract:

:We have utilized quantitative autoradiography with the GABA(A) receptor chloride channel blocker [35S]t-butylbicyclophosphorothionate ([35S]TBPS) in rodent brain sections to investigate if differential proton modulation of various GABA(A) receptor subtypes expressed in various brain regions are differentially sensitive to pH alternations. Acidic and basic pHs decreased the binding, the mean values at pH 5.4 and pH 9.4 being 17% and 76% of the binding at pH 7.4, respectively. The regional profiles of the pH effects could be divided into two types. In regions with high basal binding at pH 7.4. the pH profile was usually 'bell-shaped,' with maximal binding at pH 7.4 (type 1). In regions with low basal binding at pH 7.4, the pH profile (type 2) revealed very low binding at pH 5.4, lower sensitivity to high pH, and usually maximal binding at pH 8.4. In brain regions with type 1 pH modulation alpha1 and beta2 subunits are abundantly expressed, whereas alpha2 and beta3 subunits are abundant in type 2 regions. Therefore the alpha1beta2gamma2 and alpha2beta3gamma2 receptor subtypes are suggested to be preferentially responsible for brain regional heterogeneity of the pH modulation of [35S]TBPS binding.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Uusi-Oukari M,Kosonen P,Homanics GE,Korpi ER

doi

10.1023/b:nere.0000018849.54169.c4

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

771-80

issue

4

eissn

0364-3190

issn

1573-6903

journal_volume

29

pub_type

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