In Intact Islets Interstitial GABA Activates GABA(A) Receptors That Generate Tonic Currents in alpha-Cells
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 6, e67228- p.Article in journal (Refereed) Published
In the rat islets γ-aminobutyric acid (GABA) is produced by the β-cells and, at least, the α-cells express the GABAA receptors (GABAA channels). In this study, we examined in intact islets if the interstitial GABA activated the GABAA receptors. We used the patch-clamp technique to record whole-cell and single-channel currents and single-cell RT-PCR to identify the cell-type we recorded from, in the intact rat islets. We further identified which GABAA receptor subunits were expressed. We determined the cell-type of 43 cells we recorded from and of these 49%, 28% and 7% were α, β and δ-cells, respectively. In the remaining 16% of the cells, mRNA transcripts of more than one hormone gene were detected. The results show that in rat islets interstitial GABA activates tonic current in the α-cells but not in the β-cells. Seventeen different GABAA receptor subunits are expressed with high expression of α1, α2, α4, α6, β3, γ1, δ, ρ1, ρ2 and ρ3 subunits whereas no expression was detected for α5 or ε subunits. The abundance of the GABAA receptor subunits detected suggests that a number of GABAA receptor subtypes are formed in the islets. The single-channel and tonic currents were enhanced by pentobarbital and inhibited by the GABAA receptor antagonist SR-95531. The single-channel conductance ranged from 24 to 105 pS. Whether the single-channel conductance is related to subtypes of the GABAA receptor or variable interstitial GABA concentrations remains to be determined. Our results reveal that GABA is an extracellular signaling molecule in rat pancreatic islets and reaches concentration levels that activate GABAA receptors on the glucagon-releasing α-cells.
Place, publisher, year, edition, pages
2013. Vol. 8, no 6, e67228- p.
IdentifiersURN: urn:nbn:se:uu:diva-203228DOI: 10.1371/journal.pone.0067228ISI: 000321738400122PubMedID: 23826240OAI: oai:DiVA.org:uu-203228DiVA: diva2:635776