Abstract

In this study, we analyzed the impact that spontaneous seizures might have on the plasma membrane expression, composition and function of GABA(A) receptors (GABA(A)Rs). For this, the tissue of chronically epileptic rats was collected within 3 h of seizure occurrence (= 3 h group) or at least 24 h after seizure occurrence (>= 24 h group). A retrospective analysis of seizure frequency revealed that selecting animals on the bases of seizure proximity also grouped animals in terms of overall seizure burden with a higher seizure burden observed in the = 3 h group. A biochemical analysis showed that although animals with more frequent/recent seizures (= 3 h group) had similar levels of GABA(A)R at the plasma membrane they showed deficits in inhibitory neurotransmission. By contrast, the tissue obtained from animals experiencing infrequent seizures (>= 24 h group) had increased plasma membrane levels of GABA(A)R and showed no deficit in inhibitory function. Together, our findings offer an initial insight into the molecular changes that might help to explain how alterations in GABA(A)R function can be associated with differential seizure burden. Our findings also suggest that increased plasma membrane levels of GABA(A)R might act as a compensatory mechanism to more effectively maintain inhibitory function, repress hyperexcitability and reduce seizure burden. This study is an initial step towards a fuller characterization of the molecular events that trigger alterations in GABAergic neurotransmission during chronic epilepsy. (C) 2015 Elsevier Inc. All rights reserved.