title: The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.
abstract: Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.
authors: Department of Dermatology, University of California, Davis, CA 95616, USA.
authors: Hsin-Ya
authors: HY
authors: Yang
authors: Roch-Philippe
authors: RP
authors: Charles
authors: Edith
authors: E
authors: Hummler
authors: Deborah L
authors: DL
authors: Baines
authors: R Rivkah
authors: RR
authors: Isseroff
mesh_terms: D000818:Animals; D002465:Cell Movement; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D012964:Sodium / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics
chemical_list: D053503:Epithelial Sodium Channels; D012964:Sodium
keywords: Directional migration; ENaC; Keratinocyte; Lamellipodia