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

J Physiol. 1999 Mar 1;515 ( Pt 2)(Pt 2):439-52. doi: 10.1111/j.1469-7793.1999.439ac.x.

Abstract

1. Patch-clamp recordings were made from rat ventromedial hypothalamic neurones in slices of brain tissue in vitro. In cell-attached recordings, removal of extracellular glucose or metabolic inhibition with sodium azide reduced the firing rate of a subpopulation of cells through the activation of a 65 pS channel that was blocked by the sulphonylureas tolbutamide and glibenclamide. 2. In whole-cell patch-clamp recordings, in the absence of ATP in the electrode 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 outward current was not observed. Under these conditions, 500 microM diazoxide was 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 cytoplasm from single glucose-receptive neurones demonstrated the expression of the ATP-sensitive potassium (KATP) channel subunits Kir6.1 and SUR1 but not Kir6.2 or SUR2. 6. It is concluded that glucose-receptive neurones within the rat ventromedial hypothalamus exhibit a KATP channel current with pharmacological and molecular properties similar to those reported in other tissues.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Glucose / metabolism*
  • In Vitro Techniques
  • Male
  • Neurons / metabolism
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonylurea Receptors
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / metabolism*
  • Ventromedial Hypothalamic Nucleus / physiology

Substances

  • ATP-Binding Cassette Transporters
  • Abcc8 protein, rat
  • Abcc9 protein, rat
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • RNA, Messenger
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Adenosine Triphosphate
  • Glucose