In Intact Islets Interstitial GABA Activates GABAA Receptors That Generate Tonic Currents in α-Cells

In the rat islets gamma-aminobutyric acid (GABA) is produced by the beta-cells and, at least, the alpha-cells express the GABA(A) receptors (GABA(A) channels). In this study, we examined in intact islets if the interstitial GABA activated the GABA(A) 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 alpha, beta and delta-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 alpha-cells but not in the beta-cells. Seventeen different GABA(A) receptor subunits are expressed with high expression of alpha 1, alpha 2, alpha 4, alpha 6, beta 3, gamma 1, delta, rho 1, rho 2 and rho 3 subunits whereas no expression was detected for alpha 5 or e subunits. The abundance of the GABA(A) receptor subunits detected suggests that a number of GABA(A) receptor subtypes are formed in the islets. The single-channel and tonic currents were enhanced by pentobarbital and inhibited by the GABA(A) 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 GABA(A) 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 GABA(A) receptors on the glucagon-releasing alpha-cells.