L14 HOW DO POTASSIUM CHANNEL OPENERS STIMULATE HAIR GROWTH?
Randall VA
Department of Biomedical Sciences, University of Bradford, UNITED KINGDOM

Minoxidil, diazoxide and other related drugs have been known for many years to stimulate hair growth; indeed minoxidil is widely used as a topical hair growth-promoting agent. However, their mode of action on the hair follicle is unclear, although various suggestions, including vasoactive effects, have been made. A consistent feature is that these hair growth-promoting drugs open ATP sensitive potassium (KATP) channels in plasma membranes. Understanding how these drugs work should enable the development of more potent hair growth promoting treatments. KATP channels consist of two types of sub-unit, the sulphonurea receptor, SUR, which regulates the channel, and the pore-forming K+ inward rectifier subunit, Kir, which controls the ability of potassium ions to pass through the membrane. The regulatory SUR sub-unit has three forms, SUR1, SUR2A and SUR2B, which can combine with the two forms of the Kir sub-unit, Kir6.1 and Kir6.2. Since KATP channels in different tissues contain various combinations of these subtypes, tissues possess differing sensitivities to individual potassium channel regulators. One of the problems in understanding how the drugs work has been the lack of a reliable in vitro bioassay; results from earlier studies have been inconsistent, probably due to complications from using serum and/or streptomycin in the media. Recently, Davies et al (2005) developed an ethically sound bioassay using red deer anagen hair follicles cultured without serum or streptomycin that reflected human clinical responses in vitro. Using this bioassay, the responses to several potassium channel regulators with different specificity for potassium channels were investigated to determine which channels were present in hair follicles. These included minoxidil, diazoxide and a novel, selective Kir6.2/SUR1 potassium channel opener, NNC 55-0118, plus potassium channel blockers, tolbutamide and glibenclamide. Minoxidil and NNC 55-0118 were potent stimulators of hair growth while diazoxide was less effective. Since potassium channel blockers were able to prevent hair growth stimulation by the openers, the drugs appear to be acting directly through potassium channels in the hair follicles, independently of any possible vascular effects. As NNC 55-0118 only acts via Kir6.2/SUR1 and minoxidil does not, at least two types of KATP channels must be present. These would be channels with SUR1 and SUR2, probably SUR2B which is expressed in human dermal papilla cells, receptors. The discovery of two types of KATP channel, one of which minoxidil will not affect, could lead to the development of better hair growth treatments.