title: Effect of K+ channel openers on K+ channel in cultured human dermal papilla cells.
abstract: Minoxidil sulfate and pinacidil, well-known activators of the ATP-sensitive K+ (KATP) channel, induce hair growth in clinical studies. The opening of K+ channels is thought to be an important mechanism in the regulation of hair follicles. In the present study, we used the patch clamp technique to characterize the K+ channels and tested the effect of K+ channel openers on K+ channels in cultured human dermal papilla cells. In dermal papilla cells, the Ca(2+)-activated K+ (KCa) channel with large conductance (179.3 +/- 13.1 pS in symmetrical 150 mM K+ solutions, n = 9) was dominant and we could not observe KATP channels in cell-attached and inside-out patches. In addition, minoxidil and pinacidil failed to activate KATP or KCa channels. In inside-out membrane patches, the channel was blocked by 10 mM tetraethylammonium ion, 2 mM 4-aminopyridine to the cytosolic face of the membrane or by lowering Ca2+ using 10 mM EGTA, but not by glibenclamide. In the cell-attached patch configurations, extracellular application of 1 mM sodium nitroprusside, a nitrovasodilator, activated the KCa channel. Methylene blue (2 mM) inhibited channel activation by sodium nitroprusside. Extracellular application of 20 mM dibutyryl cGMP activated the KCa channel, suggesting that channel activation is mediated by cGMP. Nitrovasodilators, which have no effect on hair growth, now appear to activate KCa channels in dermal papilla cells. These results suggest that increased K+ permeability itself in dermal papilla cells may not be sufficient for promotion of hair growth.
authors.affiliation: Department of Pharmacy, University of Tokushima School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hamaoka
authors.forename: K
authors.initials: K
authors.lastname: Minakuchi
authors.forename: H
authors.initials: H
authors.lastname: Miyoshi
authors.forename: S
authors.initials: S
authors.lastname: Arase
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology*; D018859:Hair Follicle / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008914:Minoxidil / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D008914:Minoxidil; D020110:Pinacidil