Experimental status epilepticus alters γ‐aminobutyric acid type A receptor function in CA1 pyramidal neurons

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Abstract
There is a reduction of β‐aminobutyric acid (GABA)‐mediated inhibition in 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.