Gamma-aminobutyric acid (GABA) is known as the inhibitory neurotransmitter in the adult mammalian central nervous system (CNS). It is also produced in the islets of Langerhans in pancreas where it serves as an paracrine and autocrine signaling molecule regulating the hormone secretion of pancreatic cells through GABAA channels (1). The GABAA channel is a ligand-gated ion channel permeable to chloride and bicarbonate. When the GABAA channels are activated, they depolarize the β-cells and hyperpolarize the α-cells in the human islets, due to different intracellular chloride concentrations (2). In pancreatic islets, GABA is synthesized in the β-cells, and released by both vesicular and nonvesicular processes (3). We have recently shown GABA modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals. Moreover, both phasic and tonic GABAA channels activation were recorded in intact islet cells (4). Whereas the normal range of interstitial GABA concentration is not known, and information regarding the islets GABAA channel pharmacology is not available either. We, therefore, did whole-cell patch-clamp recordings on cells in intact human islets to further investigate the pharmacological characteristics of the native GABAA channels expressed in the islets. The results show that in 16 out of 23 cells, the GABAA channels conductance in human pancreatic islets are enhanced maximally (82 + 23 pS), when 100 nM or 1 µM GABA is applied, as compared to the channel conductance (39 + 17 pS) activated by the interstitial GABA. Among the 16 cells, channels in 9 cells desensitize in 1 µM GABA. These results support the notion that GABAA channels with very high affinity are present in the islet cells. Furthermore, the endogenous interstitial GABA concentration is in the range between 10 nM and 1 µM in islets when 20 mM glucose is present. We further examined several known GABAA channel modulators: pentobarbital, diazepam, zolpidem and propofol. The results demonstrated that 100 μM pentobarbital (15 cells), 1 μM diazepam (12 cells) and 50 μM propofol (13 cells) consistently potentiated the GABAA channels, whereas 100 nM zolpidem (10 out of 11 cells) did not. The results identify the pancreatic islet cells’ GABA channels are high-affinity, high-conducting, extrasynaptic GABAA channels.