IDENTIFICATION OF AN ATP-SENSITIVE POTASSIUM CHANNEL CURRENT IN RAT STRIATAL CHOLINERGIC INTERNEURONS

1. Whole-cell patch-clamp recordings were made from rat striatal choli nergic interneurones in slices of brain tissue in, vitro. In the absen ce of ATP in the electrode solution, these neurones were found to grad ually hyperpolarize through the induction of an outward current at -60 mV. This outward current and the resultant hyperpolarization were blo cked by the sulphonylureas tolbutamide and glibenclamide and by the ph otorelease of caged ATP within neurones. 2. This ATP-sensitive outward current was not observed when 2 mM ATP was present in the electrode s olution. Under these conditions, 500 mu M diazoxide was found to induc e an outward current that was blocked by tolbutamide. 3. Using permeab ilized patch recordings, neurones were shown to hyperpolarize in respo nse to glucose deprivation or metabolic poisoning with sodium azide (N aN3). The resultant hyperpolarization was blocked by tolbutamide. 4. I n cell-attached recordings, metabolic inhibition with 1 mar NaN3 revea led the presence of a tolbutamide-sensitive channel exhibiting a unita ry conductance of 44.1 pS. 5. Reverse transcription followed by the po lymerase chain reaction using cytoplasm from single cholinergic intern eurones demonstrated the expression of the ATP-sensitive potassium (K- ATP) channel subunits Kir6.1. and SUR1 but not Kir6.2 or SUR2. 6. It i s concluded that cholinergic interneurones within the rat striatum exh ibit a K-ATP channel current and that this channel is formed from Kir6 .1 and SUR1 subunits.