Author:

Keywords:

Amino Acid Sequence, Animals, Anions, Cattle, Cells, Cultured, Endothelium, Vascular, Enzyme Inhibitors, Ion Channels, Molecular Sequence Data, Myosin Light Chains, Myosin-Light-Chain Kinase, Phosphorylation, Research Support, Non-U.S. Gov't, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, Cell Biology, chloride channel, endothelium, cytoskeleton, myosin light chain kinase, myosin light chain phosphatase, CHLORIDE CURRENTS, CELLS, ACTIVATION, PHOSPHATASE, SUBUNIT, KINASE, CYTOSKELETON, ALPHA, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 0603 Evolutionary Biology, 3101 Biochemistry and cell biology

Abstract:

The Rho/Rho-associated kinase (ROK) pathway has been shown to modulate volume-regulated anion channels (VRAC) in cultured calf pulmonary artery endothelial (CPAE) cells. Since Rho/ROK can increase myosin light chain phosphorylation, we have now studied the effects of inhibitors of myosin light chain kinase (MLCK) or myosin light chain phosphatase (MLCP) on VRAC in CPAE. Application of ML-9, an MLCK inhibitor, inhibited VRAC, both when applied extracellularly or when dialyzed into the cell. A similar inhibitory effect was obtained by dialyzing the cells with AV25, a specific MLCK inhibitory peptide. Conversely, NIPP1(191-210), an MLCP inhibitory peptide, potentiated the activation of VRAC by a 25% hypotonic stimulus. These data indicate that activation of VRAC is modulated by MLC phosphorylation.