EXPRESSION OF GABA(A) RECEPTOR SUBUNITS IN THE HIPPOCAMPUS OF THE RATAFTER KAINIC ACID-INDUCED SEIZURES

The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes rece nt work from our laboratory on the characterization of the immunocytoc hemical distribution of these GABA(A) receptor subunits in the rat bra in and changes in immunoreactivity and mRNA expression after kainic ac id-induced status epilepticus. A heterogeneous distribution of immunor eactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha(1), alpha(2), alpha(4), alpha(5), beta(2), beta(3), gamma (2), delta. alpha(1), beta(2), and gamma(2) were about equally distrib uted in all subfields of the hippocampus; alpha(4)- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha(2) was localized to the dentate molecular layer and CA3; alpha(5 ) was found in the dendritic areas of CA1 to CA3; and beta(1) was pref erentially seen in CA2. alpha(1), beta(2), gamma(2) and delta were hig hly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactiv e proteins. Acute changes included decreases in alpha(2), alpha(5), be ta(1), beta(3), gamma(2) and delta mRNA levels (by about 25-50%), acco mpanied by increases (by about 50%) in alpha(1), alpha(4), and beta(2) messages in granule cells (after 6-12 h). Chronic changes, characteri zed by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha(2) and beta(3) subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha(1), alpha(2), alpha(4), beta(1), beta(2), beta(3) and gamma(2) in granule cells and in the molecular layer of the denta te gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all h ippocampal subfields, may reflect altered GABA-ergic transmission duri ng development of the epileptic syndrome. Increased expression of GABA (A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. H owever, the lasting preservation of alpha(1)-, beta(2)-, and gamma(2)- subunits in interneurons could provide a basis for augmented inhibitio n of GABA-ergic interneurons, leading to net disinhibition. (C) 1998 E lsevier Science B.V. All rights reserved.