Potassium Channel Conductance as a Control Mechanism in Hair Follicles.

Abstract

The opening of intracellular potassium channels is a common mechanism of action for a set of anti-hypertensive drugs that includes the hair-growth-inducing agent minoxidil. Recent work suggests potassium channel openers (PCOs) also influence hair growth. Correlative studies demonstrate that a series of PCOs including minoxidil, pinacidil, P-1075, an active pinacidil analog, RP-49,356, cromakalim, and nicorandil maintain hair growth in cultured vibrissa follicles. Studies using balding stumptail macaques verify that minoxidil, P-1075, and cromakalim but not RP-49,356 stimulate hair growth. The definition of potassium channels and documentation of drug effects on these channels is classically done using electrophysiologic techniques. Such studies require the identification and isolation of target cells. Both these are among the unsolved problems in the area of hair biology. Estimating K+ flux using 86Rb+ as a K+ tracer is an accepted method of assessing potassium channel conductance in other organ systems. Both pinacidil and RP-49,356 induce measurable Rb+ flux in isolated vibrissa follicles and a hair epithelial cell line whereas neither minoxidil nor minoxidil sulfate had measurable effects. Potassium channels have been studied successfully in other organ systems using specific pharmacologic blockers for the various channel subtypes. Blockers including glyburide, tetraethylammonium, and procaine failed to inhibit minoxidil stimulation of cultured follicles. The current explosion of knowledge on potassium channel biology, cloning of channels, and continued progress in hair biology promise to clarify the role of K+ ions in the control of hair follicles.

Medical treatments for male and female pattern hair loss

“…50 Another randomized, placebo controlled trial comparing the efficacy of topical 5% solution with topical 2% and placebo in women Table I. Minoxidil: proposed mechanisms of action Vasodilatory properties 16,38 Angiogenic properties 17 Enhanced cell proliferation and DNA synthesis 24,27 Potassium channel opener 39,40 Antiandrogen effects 41 Suppression of collagen synthesis 42,43 Immunosuppressive effects 32,35,36 demonstrated statistically significant increased hair growth in both the 5% and 2% group over the placebo group, but not necessarily in the 5% over the 2% group. 51 There was an increased occurrence of pruritus, irritation, and hypertrichosis in the 5% versus the 2% group.…”

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

“…In addition, streptomycin was included in the vibrissae study and only increased cysteine incorporation was measured, which may not equate to greater hair length. Finally, the concentration of the drugs used differed; although the glibenclamide concentrations are similar, Buhl et al (1993) used a minoxidil concentration 100-fold higher and lower tolbutamide concentrations.…”

Developmental expression and functional significance of Kir channel subunits in ureteric bud and nephron epithelia

“…There is growing evidence that K + channels may serve functions necessary for cell proliferation [33,39], and specific openers of inwardly rectifying Kir6/SUR (K ATP ) channels (pinacidil, minoxidil and cromakalim) are used clinically to stimulate hair growth in patients with alopecia [2,5]. Recently, it has been shown that these K ATP channel openers increase the mitogen-induced proliferation and DNA synthesis of liver cells [21].…”