Myosin regulation of NKCC1: effects on cAMP-mediated Cl- secretion in intestinal epithelia |
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Authors: | Hecht Gail; Koutsouris Athanasia |
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Abstract: | The basally located actin cytoskeleton has been demonstratedpreviously to regulate Cl secretion from intestinal epithelia via its effects on theNa+-K+-2Cl cotransporter (NKCC1). In nontransporting epithelia, inhibition ofmyosin light chain kinase (MLCK) prevents cell-shrinkage-induced activation of NKCC1. The aim of this study was to investigate the roleof myosin in the regulation of secretagogue-stimulated Cl secretion in intestinalepithelia. The human intestinal epithelial cell line T84 was used forthese studies. Prevention of myosin light chain phosphorylation withthe MLCK inhibitor ML-9 or ML-7 and inhibition of myosin ATPase withbutanedione monoxime (BDM) attenuated cAMP but notCa2+-mediatedCl secretion. Both ML-9 andBDM diminished cAMP activation of NKCC1. Neither apicalCl channel activity,basolateral K+ channel activity,norNa+-K+-ATPasewere affected by these agents. Cytochalasin D prevented suchattenuation. cAMP-induced rearrangement of basal actin microfilaments was prevented by both ML-9 and BDM. The phosphorylation of mosin lightchain and subsequent contraction of basal actin-myosin bundles arecrucial to the cAMP-driven activation of NKCC1 and subsequent apicalCl efflux. |
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