p38 MAP kinase modulates liver cell volume through inhibition of membrane Na+ permeability

摘要: In hepatocytes, Na+ influx through nonselective cation (NSC) channels represents a key point for regulation of cell volume. Under basal conditions, are closed, but both physiologic and pathologic stimuli lead to large increase in water influx. Since osmotic also activate mitogen-activated protein (MAP) kinase pathways, we have examined permeability volume by MAP kinases an HTC liver model. isotonic there was constitutive activity p38 that selectively inhibited SB203580. Decreases caused hypertonic exposure had no effect on p38, increases hypotonic increased tenfold. currents were small when cells media could be inhibiting kinase, thereby increasing To evaluate the potential inhibitory role more directly, dialyzed with recombinant p38alpha its upstream activator, MEK-6, which substantially volume-sensitive currents. These findings indicate contributes low necessary maintenance volume, negatively modulates set channel opening. Thus, functional interactions between ion may represent important target modifying functions.