Zinc inhibition of gamma-aminobutyric acid(A) receptor function is decreased in the cerebral cortex during pilocarpine-induced status epilepticus

Functional modulation of gamma-aminobutyric acid(A) (GABA(A)) receptors by Zn2+, pentobarbital, neuroactive steroid alphaxalone, and flunitrazepam was studied in the cerebral cortex and cerebellum of rats undergoing status ep ilepticus induced by pilocarpine. Under control conditions, Zn2+ dose-depen dently inhibited muscimol-stimulated uptake of Cl-36(-) in cortical and cer ebellar membranes. However, Zn2+ inhibition of stimulated Cl-36(-) uptake w as selectively decreased in the cortex (but not in the cerebellum) 1 to 2 h after the onset of status epilepticus. This loss of Zn2+ response in the c ortex appeared to be selective to Zn2+ only, because pentobarbital-, alphax alone-, or flunitrazepam enhancement of muscimol-stimulated Cl-36(-) uptake did not change in this brain region either at 1 or 2 h after seizures. Bec ause this loss of Zn2+ response in the cortex was apparent only about 1 h a fter the onset of status epilepticus but not earlier, we tested whether sta tus epilepticus was critical for the development of the loss of Zn2+ respon se. We found that, in rats where status epilepticus was terminated by diaze pam within 30 min after seizure onset, Zn2+ response was preserved in the c ortex. These findings suggest that continuous seizures of pilocarpine-induc ed status epilepticus caused a rapid and selective decrease in Zn2+ inhibit ion of GABA(A) receptor function in the cortex. The possible relevance of s uch rapid seizure-induced GABA(A) receptor plasticity in the cerebral corte x is discussed.