Sulphonylureas reverse hypoxia induced K(+)-conductance increase in substantia nigra pars reticulata neurones

Neuroreport. 1996 Nov 4;7(15-17):2513-7. doi: 10.1097/00001756-199611040-00022.

Abstract

Membrane potentials were recorded from neuronal somata in the substantia nigra pars reticulata of the rat midbrain slice using the whole-cell patch-clamp technique. Hypoxia induced a consistent decrease in input resistance often accompanied by membrane hyperpolarization and cessation of firing. The membrane hyperpolarization was mediated by K+ as indicated by its reversal potential at -88 +/- 9 mV, which is close to the equilibrium potential of K+. The hypoxic response was not sensitive to 1 microM tetrodotoxin or superfusion with Ca2(+)-free medium. While glibenclamide at 30 microM and tolbutamide at 300 microM had no effect on the resting membrane properties of the neurones, these sulphonylureas reversed the hypoxia-induced membrane hyperpolarization and restored firing. Inclusion of 2 mM of ATP in the recording pipette also prevented the hyperpolarization. These observations suggest that post-synaptic ATP-sensitive potassium channels exist on the GABA neurones of SNR and that these channels are activated in energy-depleting conditions exemplified by hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glyburide / pharmacology*
  • Hypoxia / physiopathology*
  • Membrane Potentials / drug effects*
  • Potassium Channels / drug effects*
  • Rats
  • Substantia Nigra / drug effects*
  • Tetrodotoxin / pharmacology

Substances

  • Potassium Channels
  • Tetrodotoxin
  • Glyburide