Gamma-aminobutyric acid (GABA) has been shown to be secreted from the islets of Langerhans in pancreas where it serves as an important paracrine and autocrine signaling molecule regulating the pancreatic cells excitability through GABAA channels (Rorsman et al., 1989). The GABAA channel is a ligand-gated ion channel permeable to chloride and bicarbonate. When the GABAA channels are activated, they depolarize the b-cell and hyperpolarize the a and d-cell in the human islets, due to different intracellular chloride concentrations (Braun et al., 2010). In pancreatic islets, GABA is synthesized in the b-cells, and released by both vesicular and nonvesicular processes (Braun et al., 2007). We have recently shown GABA effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals. Moreover, both phasic and tonic GABAA channels activation were recorded in intact islets (J. Taneera, 2012). However, the interstitial GABA concentration is not known, and information regarding the islets GABAA channel pharmacology is not available. We, therefore, applied whole-cell patch-clamp recordings on intact human islets to further investigate the pharmacological characteristics of the native GABAA channels expressed in the islets. The results show that the GABAA channels opening in human pancreatic islets are enhanced relative to the baseline activity when 100 nM GABA is applied but the channels do desensitize in 1 mM GABA. These results support the notion that GABAA channels with very high affinity are present in the islets. Furthermore, the endogenous intra-islet GABA concentration is lower than 100 nM in islets when 20 mM glucose is present. We further examined the pharmacology of these channels. The results demonstrated that pentobarbital, diazepam and propofol consistently potentiated the GABAA channels, whereas zolpidem did not, which differs from the pharmacology in CNS.