PROPAGATION OF MECHANICALLY INDUCED INTERCELLULAR CALCIUM WAVES VIA GAP-JUNCTIONS AND ATP RECEPTORS IN RAT-LIVER EPITHELIAL-CELLS

Mechanical stimulation was used to initiate Ca2+ waves in rat liver ep ithelial cells in order to ascertain the degree to which gap junctiona l intercellular communication (GJIC) is involved in communication of C a2+ to adjacent cells and to assess alternative C2+ signaling pathways that may be present between these cells. In both WB-F344 cells, which show a high degree of GJIC, and WB-aB1 cells, which are GJIC deficien t, mechanical stimulation of a single cell induced a Ca2+ wave which p ropagated away from the point of stimulation, across cell borders, to neighboring cells directly or indirectly in contact with the stimulate d cell. In addition, the Ca2+ wave was transmitted to nearby isolated cells that exhibited no direct or indirect contact with the stimulated cell. Treatment of cells with 18 beta-glycyrrhetinic acid, a compound that has been shown to block GJIC, did not significantly affect propa gation of the Ca2+ wave. In contrast, treatment with suramin, a P-2-pu rinergic receptor inhibitor, significantly reduced both the rate and t he extent of Ca2+ wave propagation in WB-F344 cells and completely blo cked its propagation in WB-aB1 cells. Cotreatment with suramin and gly cyrrhetinic acid was found to completely block the mechanically induce d Ca2+ wave in both cell lines. These studies indicate that mechanical ly induced cell injury in rat liver epithelial cells initiates signali ng through at least two pathways, involving intercellular communicatio n via gap junctions and extracellular communication via ATP activation of purinergic receptors. (C) 1997 Academic Press.