title: K+ channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of KCa, KATP, and KV channels?
abstract: Acetylcholine released from cholinergic nerves is involved in heat loss responses of cutaneous vasodilation and sweating. K(+) channels are thought to play a role in regulating cholinergic cutaneous vasodilation and sweating, though which K(+) channels are involved in their regulation remains unclear. We evaluated the hypotheses that 1) Ca(2+)-activated K(+) (KCa), ATP-sensitive K(+) (KATP), and voltage-gated K(+) (KV) channels all contribute to cholinergic cutaneous vasodilation; and 2) KV channels, but not KCa and KATP channels, contribute to cholinergic sweating. In 13 young adults (24 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with: 1) lactated Ringer (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). At all sites, cholinergic cutaneous vasodilation and sweating were induced by coadministration of methacholine (0.0125, 0.25, 5, 100, and 2,000 mM, each for 25 min). The methacholine-induced increase in CVC was lower with the KCa channel blocker relative to Control at 0.0125 (1 ± 1 vs. 9 ± 6%max) and 5 (2 ± 5 vs. 17 ± 14%max) mM methacholine, whereas it was lower in the presence of KATP (69 ± 7%max) and KV (57 ± 14%max) channel blocker compared with Control (79 ± 6%max) at 100 mM methacholine. Furthermore, methacholine-induced sweating was lower at the KV channel blocker site (0.42 ± 0.17 mg·min(-1)·cm(-2)) compared with Control (0.58 ± 0.15 mg·min(-1)·cm(-2)) at 2,000 mM methacholine. In conclusion, we show that KCa, KATP, and KV channels play a role in cholinergic cutaneous vasodilation, whereas only KV channels contribute to cholinergic sweating in normothermic resting humans.
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Louie
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: McNeely
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada.
authors.forename: Sarah Yan
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada.
authors.forename: My-An
authors.initials: MA
authors.lastname: Tran
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Canada gkenny@uottawa.ca.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D012867:Skin / Q000098:blood supply; D013546:Sweating / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D055815:Young Adult
chemical_list: D054086:KATP Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D000109:Acetylcholine
keywords: hyperpolarization; potassium channel; sweat secretion; thermoregulation