POTASSIUM CHANNEL DYSFUNCTION IN HYPOTHALAMIC GLUCOSE-RECEPTIVE NEURONS OF OBESE ZUCKER RATS

1. We have shown, using intracellular and cell-attached recordings, th at glucose-receptive (GR) neurones of obese Zucker rats exhibit abnorm al electrophysiological responses to changes in extracellular glucose concentration, whereas GR neurones of lean Zucker and control rats res pond normally. 2. In inside-out recordings from obese rat GR neurones it was shown that the 150 pS ATP-sensitive K+ (K-ATP) and the 160 pS c alcium-activated K+ (K-Ca) channels were absent, whereas both were pre sent in GR neurones of lean Zucker and control rats. 3. The potassium channel most frequently observed in inside-out patches from obese GR n eurones was characterized by a conductance of 213 pS, was activated by raising internal calcium and inhibited by application of internal ATP . This channel (which ave have termed KS,) was not observed in lean or control rat GR neurones. 4. Tolbutamide (100 mu M) was found to induc e no effect or to elicit a small depolarization of obese rat GR neuron es in the absence of glucose, in contrast to its clear excitatory acti ons on control or lean Zucker GR neurones. 5. Intracellular, cell-atta ched and inside-out recordings from obese rat non-GR neurones showed t hat there was no alteration in their membrane properties or firing cha racteristics or in the characteristics of the large-conductance calciu m-activated K+ channel (K-Ca) present in these neurones as compared wi th lean and control rats. 6. It is concluded that the K-fa channel is specific to GR neurones of obese Zucker rats and that the presence of this channel coupled with the absence of K-ATP and K-Ca channels resul ts in the abnormal glucose-sensing response of these neurones.