Acute loss of cell–cell communication caused by G protein-coupled receptors: A critical role for c-Src

Gap junctions mediate cell–cell communica-tion in almost all tissues, but little is known about their regulation by physiological stimuli. Using a novel sin-gle-electrode technique, together with dye coupling studies, we show that in cells expressing gap junction protein connexin43, cell–cell communication is rapidly disrupted by G protein–coupled receptor agonists, no-tably lysophosphatidic acid, thrombin, and neuropep-tides. In the continuous presence of agonist, junctional communication fully recovers within 1–2 h of receptor stimulation. In contrast, a desensitization-defective G protein–coupled receptor mediates prolonged uncou-pling, indicating that recovery of communication is con-trolled, at least in part, by receptor desensitization. Ag-onist-induced gap junction closure consistently follows inositol lipid breakdown and membrane depolarization and coincides with Rho-mediated cytoskeletal remod-eling. However, we find that gap junction closure is in-dependent of C