Experimental status epilepticus alters gamma-aminobutyric acid type A receptor function in CA1 pyramidal neurons.
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.
Kapur
J
J
Department of Neurology, Medical College of Virginia, Richmond, USA.
Coulter
D A
DA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D017966:Pyramidal Cells / Q000737:chemistry* / Q000503:physiopathology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology; D013226:Status Epilepticus / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid