HIPPOCAMPAL CONNEXIN-43 EXPRESSION IN HUMAN COMPLEX PARTIAL SEIZURE DISORDER

An increase in the cellular product-ion of gap junction proteins and i ncreased numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have been proposed as a possible mechanism underlying synchronization of discharge. To study this issue, both Northern and W estern blot analyses of the gap junction protein connexin 43 mRNA and protein abundance were performed on hippocampal tissue resected from p atients presenting with a complex partial seizure disorder arising fro m the medial temporal area and the hippocampus ill particular, Samples from 15 patients with medically intractable seizures were compared to those from 5 nonepileptic patients requiring; temporal lobectomy in L ife-threatening situations. Six of the 15 epileptic patients underwent noninvasive electrographic recording, whereas the remaining 9 patient s required intracerebral electrodes for extraoperative recording and t herefore showed a more discrete focality than the noninvasive recordin gs. A decline in the mean levels of connexin 43 mRNA expressed predomi nantly in astrocytes was noted in the epileptic patient groups, partic ularly for those cases requiring intracranial electrode placement wher e ic tal onset was more clearly established to be intrahippocampal., Q uantitation of connexin 43 protein in both epileptogenic and nonepilep togenic hippocampal tissues showed no significant differences in expre ssion. Although mean values for mRNA showed a decline, clinical outcom es postoperatively showed no correlation with either mRNA or protein e xpression individually in our epileptic population The findings indica te that there is effectively no upregulation of mRNA and no increased production of connexin 43 protein in response to the development of ep ileptogenicity. Rather it appears the influence of gap junctions as a substrate of epileptogenicity in ally mechanism(s) underlying synchron y or electrical propagation may be a function of the dynamic state (op en versus closed) of the membrane-bound gapjunction. (C) 1997 Academic Press.