ISSN:
1524-475X
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Restitution is the process by which superficial interruptions in the gastrointestinal mucosa are repaired by the flattening and spreading of epithelial cells surrounding the damage. During this process, mucosal epithelial cells undergo extensive reshaping and cytoskeletal remodeling. K+ channels, located primarily on the basolateral surface of gut epithelial cells, are central to both actin polymerization, via their control of membrane potential, and cell volume regulation. We questioned whether K+ channels are involved in restitution using an in vitro model of intestinal epithelium, monolayers of the human colon carcinoma cell line T84. We report that pharmacologic K+ channel inhibition accelerates wound healing in T84 cell monolayers. Both Ca++-dependent and constitutively active channels are involved, as indicated by the sensitivity to clotrimazole, charybdotoxin, and barium. The ability of clotrimazole to accelerate wound resealing was also observed in Caco-2 cell sheets. Pharmacologic stimulation of K+ channel activity had no effect on the repair rate. Analysis of the resealing process by time lapse and confocal microscopy revealed that K+ channel inhibitors abolished the initial wound retraction, briefly accelerated the repair rate, and altered the shape of the cell sheet abutting the injury during the early phase of resealing. We hypothesize that K+ channel inactivation interrupts the coregulation of f-actin polymerization and volume control that is initiated by the healing process.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1067-1927.2004.012509.x
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