Novel and Established Potassium Channel Openers Stimulate Hair Growth In Vitro: Implications for their Modes of Action in Hair Follicles

Although ATP-sensitive potassium (KATP) channel openers, e.g., minoxidil and diazoxide, can induce hair growth, their mechanisms require clarification. Improved drugs are needed clinically. but the absence of a good bioassay hampers research. KATP channels from various tissues contain subtypes of the regulatory sulfonylurea receptor, SUR, and pore-forming, K+ inward rectifier subunits, Kir6.X, giving differing sensitivities to regulators. Therefore, the in vitro effects of established potassium channel openers and inhibitors (tolbutamide and glibenclamide), plus a novel, selective Kir6.2/SUR1 opener, NNC 55-0118, were assessed on deer hair follicle growth in serum-free median without streptomycin. Minoxidil (0.1-100 μM, p<0.001), NNC 55-0118 (1 mM, p<0.01; 0.1, 10, 100 μM, p<0.001), and diazoxide (10 μM, p<0.01) increased growth. Tolbutamide (1 mM) inhibited growth (p<0.001) and abolished the effect of 10 μM minoxidil, diazoxide and NNC 55-0118; glibenclamide (10 μM) had no effect, but prevented stimulation by 10 μM minoxidil. Phenol red stimulated growth (p<0.001), but channel modulator responses remained unaltered. Thus, deer follicles offer a practical, ethically advantageous in vitro bioassay that reflects clinical responses in vivo. The results indicate direct actions of KATP channel modulators within hair follicles via two types of channels, with SUR 1 and SUR 2, probably SUR2B, sulfonylurea receptors.