RGDS TETRAPEPTIDE AND HIPPOCAMPAL IN-VITRO KINDLING IN RATS - EVIDENCE FOR INTEGRIN-MEDIATED PHYSIOLOGICAL STABILITY

We have examined a potential role for integrins in an animal model of epileptogenesis termed in vitro kindling. Integrins mediate cell-cell and cell-matrix interactions, and also participate in the transduction of information from the extracellular environment to the intra-cellul ar milieu. As many extracellular matrix (ECM) molecules contain the co nserved amino acid sequence arg-gly-asp-ser (RGDS) at the integrin rec ognition site, integrin-ECM binding can be disrupted using RGDS peptid es. Hippocampal slices were washed in either RGDS, gly-gly-gly-gly (GG GG), vehicle or artificial cerebral spinal fluid (ACSF) for 1 h prior to in vitro kindling. Baseline electrophysiological responses were una ltered by RGDS peptide. The RODS-treated slices displayed a significan t decrease in the rate of spontaneous bursts, whereas the period of sp ontaneous bursting increased dramatically. Our results indicate that t he competitive peptide, RGDS, changed hippocampal slice excitability o ver time, indicating that interference with ECM-integrin binding may a lter neuronal signaling through an RGDS binding site. (C) 1997 Elsevie r Science Ireland Ltd.