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.

Keywords: hyperpolarization; potassium channel; sweat secretion; thermoregulation.

Fig. 1.

Cutaneous vascular conductance (A) and sweat rate (B) measured at Baseline. Data are presented as means ± 95% confidence interval. The four intradermal forearm sites were perfused with either 1) lactated Ringer (Control), 2) a nonspecific Ca²⁺-activated K⁺ (K_Ca) channel blocker, 3) a selective ATP-sensitive K⁺ (K_ATP) channel blocker, or 4) a nonspecific voltage-gated K⁺ (K_V) channel blocker. No between-site difference in sweat rate was observed (P = 0.33 for a main effect of treatment site).

Fig. 2.

Change (Δ) in cutaneous vascular conductance from Baseline to each dose of methacholine. Data are presented as means ± 95% confidence interval. The four intradermal forearm sites were perfused with either 1) lactated Ringer (Control), 2) a nonspecific Ca²⁺-activated K⁺ (K_Ca) channel blocker, 3) a selective ATP-sensitive K⁺ (K_ATP) channel blocker, or 4) a nonspecific voltage-gated K⁺ (K_V) channel blocker. *Control vs. K_Ca channel blocker (P ≤ 0.05); †Control vs. K_ATP channel blocker (P ≤ 0.05); ‡Control vs. K_V channel blocker (P ≤ 0.05).

Fig. 3.

Change (Δ) in sweat rate from Baseline to each dose of methacholine. Data are presented as means ± 95% confidence interval. The four intradermal forearm sites were perfused with either 1) lactated Ringer (Control), 2) a nonspecific Ca²⁺-activated K⁺ (K_Ca) channel blocker, 3) a selective ATP-sensitive K⁺ (K_ATP) channel blocker, or 4) a nonspecific voltage-gated K⁺ (K_V) channel blocker. †Control vs. K_ATP channel blocker (P ≤ 0.05); ‡Control vs. K_V channel blocker (P ≤ 0.05).

Fig. 4.

Change (Δ) in cutaneous vascular conductance (A) and sweat rate (B) from Baseline to Peak observed during methacholine administration. Data are presented as means ± 95% confidence interval. The four intradermal forearm sites were perfused with either 1) lactated Ringer (Control), 2) a nonspecific Ca²⁺-activated K⁺ (K_Ca) channel blocker, 3) a selective ATP-sensitive K⁺ (K_ATP) channel blocker, or 4) a nonspecific voltage-gated K⁺ (K_V) channel blocker.

Fig. 5.

Change (Δ) in cutaneous vascular conductance from 100 to 2,000 mM of methacholine administration. Data are presented as means ± 95% confidence interval. There are four intradermal sites perfused with either 1) lactated Ringer (Control), 2) a nonspecific Ca²⁺-activated K⁺ (K_Ca) channel blocker, 3) a selective ATP-sensitive K⁺ (K_ATP) channel blocker, or 4) a nonspecific voltage-gated K⁺ (K_V) channel blocker. Each P value is for the difference between 100 and 2,000 mM of methacholine.