The suprachiasmatic nucleus (SCN) is considered to be an endogenous circadian pacemaker. Previous studies have suggested functional roles of gamma-aminobutyric acid (GABA) in the control of circadian rhythms. In this study, the responses to applied GABA in cultured SCN neurons dissociated from postnatal rat hypothalamus were investigated using whole-cell voltage-clamp techniques. GABA and muscimol induced a large current response (EC50 values 5.3 and 1.6 microM, respectively), which was blocked by the GABAA antagonist bicuculline. This current response was also blocked by Zn2+ (0.5-50 microM) in a concentration-dependent manner, but was not potentiated by diazepam (10 microM) or ethanol (21 mM). These characteristics seem to correspond to those of GABAA receptors that lack gamma-type subunits.