Potassium channel openers accelerate epidermal barrier recovery.
BACKGROUND
Maintenance of a competent permeability barrier in the face of external and internal stressors requires signals between the stratum corneum interface and the metabolic machinery in the underlying nucleated layers. For example, reductions in the ion gradients for Ca2+ after acute barrier disruption stimulate lamellar body (LB) secretion, a response required to restore barrier homeostasis. Although alterations in external K+ levels also regulate barrier recovery after acute insults, the mechanisms whereby K+ regulates barrier function remain unknown.


OBJECTIVE
To evaluate effects of regulators of K+ channels on barrier homeostasis in hairless mice.


METHODS
We tested a number of chemically different drugs that alter intracellular K+ levels. Results Single applications of either K+ channel openers (i.e. 1-EBIO, minoxidil, diazoxide) or the K+ ionophore, valinomycin, accelerated barrier recovery after acute insults to murine skin, paralleled by a reduction in intracellular K+ levels in cultured human keratinocytes. In contrast, applications of K+ channel blockers (i.e. gilbenclamide, dequalinium) delayed barrier recovery. Alterations in intracellular K+ regulated barrier homeostasis by either stimulating (reduced K+) or inhibiting (elevated K+) LB secretion. Finally, development of epidermal hyperplasia, a downstream consequence of barrier disruption, was also inhibited by agents that reduce intracellular K+ levels.


CONCLUSIONS
These results demonstrate that changes in K+ levels that can be presumed to occur after barrier disruption signal metabolic responses, i.e. LB secretion, which accelerates normalization of barrier function.
Denda
M
M
Shiseido Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan. mitsuhiro.denda@to.shiseido.co.jp
Tsutsumi
M
M
Inoue
K
K
Crumrine
D
D
Feingold
K R
KR
Elias
P M
PM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000078404:Epidermal Cells; D006706:Homeostasis / Q000187:drug effects*; D006965:Hyperplasia / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D011188:Potassium