Glucose-receptive neurones in the rat ventromedial hypothalamus express K-ATP channels composed of Kir6.1 and SUR1 subunits

1. Patch-clamp recordings were made from rat ventromedial hypothalamic neur ones in slices of brain tissue in vitro. In cell-attached recordings, remov al of extracellular glucose or metabolic inhibition with sodium azide reduc ed the firing rate of a subpopulation of cells through the activation of a 65 pS channel that was blocked by the sulphonylureas tolbutamide and gliben clamide. 2. In whole-cell patch-clamp recordings, in the absence of ATP in the elect rode solution, glucose-receptive neurones gradually :hyperpolarized due to the induction of an outward current at -60 mV. This outward current and the resultant hyperpolarization were blocked by the sulphonylureas tolbutamide and glibenclamide. 3. In recordings where the electrode solution contained 4 mM ATP, this outw ard current was not observed. Under these conditions, 500 mu M diazoxide wa s found to induce an outward current that was blocked by tolbutamide. 4. In cell-attached recordings diazoxide and the active fragment of leptin (leptin 22-56) reduced the firing rate of glucose-receptive neurones by the activation of a channel with similar properties to that induced by removal of extracellular glucose. 5. Reverse transcription followed by the polymerase chain reaction using cy toplasm from single glucose-receptive neurones demonstrated the expression of the ATP-sensitive potassium (K-ATP) channel subunits Kir6.1 and SUR1 but not Kir6.2 or SURE. 6. It is concluded that glucose-receptive neurones within the rat ventromed ial hypothalamus exhibit a K-ATP channel current with pharmacological and m olecular properties similar to those reported in other tissues.