Experimental status epilepticus alters gamma-aminobutyric acid type A receptor function in CA1 pyramidal neurons

Ann Neurol. 1995 Dec;38(6):893-900. doi: 10.1002/ana.410380609.

Abstract

There is a reduction of gamma-aminobutyric acid (GABA)-mediated inhibition of the CA1 pyramidal region of the hippocampus during status epilepticus (SE). The cellular basis of this loss of GABA-mediated inhibition is not known. This study tested the possibility that GABA type A (GABAA) receptor function in CA1 pyramidal neurons was reduced or blocked during SE, at least in part by postsynaptic cellular mechanisms. GABAA receptor currents (IGABA) were studied by whole-cell patch-clamp techniques in CA1 pyramidal neurons acutely dissociated from rats undergoing lithium/pilocarpine-induced limbic status epilepticus (SE neurons) and from naive rats (naive neurons). SE neurons had more depolarized resting membrane potential (-17.3 mV) compared with naive neurons (-56 mV). IGABA was absent in 47% of SE neurons and reduced in 55% of the remainder, compared with naive neurons. The reduction in IGABA in SE neurons resulted from a combination of factors, including reduced potency and reduced efficacy of GABA in activating chloride channels, and diminished driving force for the GABA-induced chloride currents once activated. These postsynaptic cellular mechanisms resulted in a net reduction or loss in GABA-mediated inhibition and may explain previous in vivo findings reporting a loss of inhibition in hippocampus during limbic SE.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Chloride Channels / physiology
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Female
  • Hippocampus / cytology
  • Hippocampus / physiopathology
  • Male
  • Membrane Potentials / physiology
  • Pyramidal Cells / chemistry*
  • Pyramidal Cells / physiopathology
  • Rats
  • Receptors, GABA-A / physiology*
  • Seizures / physiopathology
  • Status Epilepticus / physiopathology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Chloride Channels
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid