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 intracellular milieu. As many extracellular matrix (ECM) molecules contain the conserved amino acid sequence arg-gly-asp-ser (RGDS) at the integrin recognition site, integrin-ECM binding can be disrupted using RGDS peptides. Hippocampal slices were washed in either RGDS, gly-gly-gly-gly (GGGG), vehicle or artificial cerebral spinal fluid (ACSF) for 1 h prior to in vitro kindling. Baseline electrophysiological responses were unaltered by RGDS peptide. The RGDS-treated slices displayed a significant decrease in the rate of spontaneous bursts, whereas the period of spontaneous bursting increased dramatically. Our results indicate that the competitive peptide, RGDS, changed hippocampal slice excitability over time, indicating that interference with ECM-integrin binding may alter neuronal signaling through an RGDS binding site.