Stimulation of Cl conductance by minoxidil sulfate and K conductance by minoxidil in eccrine clear cells.
Minoxidil sulfate (MXS), an antihypertensive agent and hair growth promoter, has been reported to stimulate K channels in vascular smooth muscle cells. We now report that MXS stimulates whole cell Cl currents, whereas minoxidil (MX) stimulates K currents in dissociated eccrine clear cells. Using whole cell clamp techniques we observed that: 1) 1 mM MXS stimulated sweat secretion in vitro; 2) MXS depolarized the membrane potential by as much as 40 mV; 3) MXS stimulated membrane conductance, increased inward current and shifted the reversal potential to the right when physiological electrolyte solutions were used; 4) in symmetrical Cl (Cl/Cl) solutions without permeable cations, MXS induced outwardly rectifying current-voltage (I-V) relationships; 5) in the Cl/Cl solutions, the MXS-induced current responses to imposed voltage pulses showed time-dependent activation, especially at the depolarizing potentials; 6) the reversal potential of the MXS-stimulated I-V curves in the Cl/Cl solutions shifted to the right by 55 mV when [Cl] in the bath was decreased from 157 to 7 mM; 7) MXS did not elevate cytosolic Ca or cAMP, although prolonged exposure to a Ca-free solution abolished the effect of MXS and 8) MXS-stimulated conductance was partially inhibited by diphenylamine-2-carboxylic acid, a blocker of Cl channels. The data suggest that MXS stimulates Cl channels, most likely depolarization-activated, outwardly rectifying channels. In contrast, the parent compound MX hyperpolarized the membrane potential and stimulated outward current without elevating cytosolic Ca and was independent of extracellular Ca, suggesting that MX stimulates Ca-insensitive K currents.
Ohtsuyama
M
M
Marshall Dermatology Research Laboratories, Department of Dermatology, University of Iowa College of Medicine, Iowa City.
Sato
F
F
Toyomoto
T
T
Sato
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004439:Eccrine Glands / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008564:Membrane Potentials / Q000187:drug effects; D008914:Minoxidil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013542:Sweat / Q000378:metabolism
D018118:Chloride Channels; D003470:Culture Media; D015221:Potassium Channels; C039516:minoxidil sulfate ester; D008914:Minoxidil; D000242:Cyclic AMP; D002118:Calcium