EXPERIMENTAL STATUS EPILEPTICUS ALTERS GAMMA-AMINOBUTYRIC-ACID TYPE-ARECEPTOR FUNCTION IN CA1 PYRAMIDAL NEURONS

There is a reduction of gamma-aminobutyric acid (GABA)-mediated inhibi tion in the CA1 pyramidal region of the hippocampus during status epil epticus (SE). The cellular basis of this loss of GABA-mediated inhibit ion is not known. This study tested the possibility that GABA type A ( GABA(A)) receptor function in CA1 pyramidal neurons was reduced or blo cked during SE, at least in part by postsynaptic cellular mechanisms. GABA(A) receptor currents (I-GABA) Were studied by whole-cell patch-cl amp techniques in CA1 pyramidal neurons acutely dissociated from rats undergoing lithium/pilocarpine-induced limbic status epilepticus (SE n eurons) and from naive rats (naive neurons). SE neurons had more depol arized resting membrane potential (-17.3 mV) compared with naive neuro ns (-56 mV). I-GABA Was absent in 47% of SE neurons and reduced in 55% of the remainder, compared with naive neurons. The reduction in I-GAB A in SE neurons resulted from a combination of factors, including redu ced potency and reduced efficacy of GABA in activating chloride channe ls, and diminished driving force for the GABA-induced chloride current s once activated. These postsynaptic cellular mechanisms resulted in a net reduction or loss in GABA-mediated inhibition and may explain pre vious in vivo findings reporting a loss of inhibition in hippocampus d uring limbic SE.