Abstract
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.
Highlights
The pancreatic islets consist of four major cell types: the glucagon-secreting a-cells, the insulin-secreting b-cells, the somatostatin-secreting d-cells and the polypeptide-producing PPcells
Gammaaminobutyric acid (GABA) is formed by the enzyme glutamate decarboxylase (GAD) which catalyses the formation of GABA from glutamate and is located both in the cytoplasm and in synaptic-like vesicles [7,8,9,10,11]
In intact rat pancreatic islets, that interstitial GABA generates tonic currents in the a-cells when the islets are exposed to 20 mM glucose
Summary
The pancreatic islets consist of four major cell types: the glucagon-secreting a-cells, the insulin-secreting b-cells, the somatostatin-secreting d-cells and the polypeptide-producing PPcells. In addition to the hormones, the cells release small molecules that may act in an auto or paracrine manner [1,2]. GABA is thought to act in an auto and paracrine manner on the islet cells to modulate hormone secretion [6,12,13,14,15,16,17]. GABA activates ionotropic GABAA and metabotropic GABAB receptors in the plasma membrane of the islet cells [6,14,18]. There are many subtypes of GABAA receptors whereas only one GABAB receptor has been described so far [20]. The physiological and pharmacological properties of the receptors are determined by the subunit-types that form the GABAA receptors [21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
