RGD Reference Report - Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors. - Rat Genome Database

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Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors.

Authors: Neelands, T R  Macdonald, R L 
Citation: Neelands TR and Macdonald RL, Mol Pharmacol. 1999 Sep;56(3):598-610. doi: 10.1124/mol.56.3.598.
RGD ID: 405650343
Pubmed: PMID:10462548   (View Abstract at PubMed)
DOI: DOI:10.1124/mol.56.3.598   (Journal Full-text)

mRNA encoding the recently cloned gamma-aminobuytyric acid(A) receptor (GABAR) pi subunit is expressed in the hippocampus and in several non-neuronal tissues including the uterus and ovaries. Whereas native GABARs are pentamers composed primarily of alphabetagamma, alphabetadelta, or alphabetaepsilon subunits, it has not been demonstrated clearly that the pi subunit incorporates into functional GABARs to form alphabetapi receptors and, if so, with what properties. We provide electrophysiological evidence that the pi subunit can coassemble with either alpha5beta3 or alpha5beta3gamma3 subunits to produce recombinant GABARs with distinct pharmacological and biophysical properties. Compared with alpha5beta3 receptors, GABARs produced by coexpression of alpha5beta3pi subunits had a lower GABA EC(50) value, were enhanced to a lesser extent by loreclezole, had different IC(50) values for pregnenolone sulfate and lanthanum, and were insensitive to benzodiazepines. Incorporation of both pi and gamma3 subunits into an alpha5beta3gamma3pi isoform was suggested by reduced enhancement by diazepam and a high zinc IC(50) value. Current-voltage relations for the alpha5beta3pi subunit combination outwardly rectified more than currents from alpha5beta3gamma3 but less than alpha5beta3 combination GABARs. Single-channel alpha5beta3 GABAR currents had a main conductance state of 15.2 picoSeimens (pS). Coexpression of the pi subunit with alpha5beta3 subtypes increased the conductance level to 23.8 pS, similar to the conductance level of alpha5beta3gamma3 GABARs (26.9 pS). We conclude that the pi subunit coassembles with alpha, beta, and gamma subunits to form functional alphabetapi or alphabetagammapi GABARs and, thus, could have a significant impact on the function of native GABARs expressed in the brain or non-neuronal tissue.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gabra5RatGABA-A receptor activity enablesIDA PMID:10462548UniProt 
Gabrb3RatGABA-A receptor activity enablesIDA PMID:10462548UniProt 
Gabrg3RatGABA-A receptor activity enablesIDA PMID:10462548UniProt 
Gabra5RatGABA-gated chloride ion channel activity enablesIDA PMID:10462548UniProt 
Gabrb3RatGABA-gated chloride ion channel activity enablesIDA PMID:10462548UniProt 
Gabrg3RatGABA-gated chloride ion channel activity enablesIDA PMID:10462548UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Gabra5  (gamma-aminobutyric acid type A receptor subunit alpha 5)
Gabrb3  (gamma-aminobutyric acid type A receptor subunit beta 3)
Gabrg3  (gamma-aminobutyric acid type A receptor subunit gamma 3)


Additional Information