A possible role for membrane depolarization in epithelial wound healing.
Linear narrow wounds produced on cultured bovine corneal endothelial monolayers heal by actin cable formation at the wound border and lamellar crawling of cells into the injured area. We report the novel finding that membrane potential depolarization occurs at the leading edge of wounds and gradually extends inward toward the neighboring cells. We have determined that the replacement of extracellular Na(+) by choline and the incorporation of phenamil, an inhibitor of the epithelial Na(+) channel (ENaC), provoke a decrease in the actin cable and depolarization areas and in the lamellar activity of the wound edges. To the contrary, extracellular Li(+) can successfully replace Na(+) in the determination of the depolarization and cytoskeletal responses. This finding supports the idea that membrane depolarization, not the increase in intracellular Na(+) concentration, is responsible for the formation of the actin cable, a result that is in agreement with previous evidence showing that nonspecific depolarization of the plasma membrane potential (PMP) of epithelial cells may promote characteristic cytoskeletal rearrangements per se (Chifflet S, Hernandez JA, Grasso S, and Cirillo A. Exp Cell Res 282: 1-13, 2003). We suggest that spontaneous depolarization of the PMP of the cells at the wound borders determined by a rise in the ENaC activity of these cells constitutes an additional factor in the intermediate cellular processes leading to wound healing in some epithelia.
Chifflet
Silvia
S
Departomento de Bioquímica, Facultad de Medicina, Universidad de la República, Gral Flores 2125, 11800 Montevideo, Uruguay. schiffle@mednet.org.uy
Hernández
Julio A
JA
Grasso
Silvina
S
D000199:Actins / Q000502:physiology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology / Q000502:physiology; D004728:Endothelium, Corneal / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D000199:Actins; C047088:phenylamil; D000584:Amiloride; D012964:Sodium; D002794:Choline