TEA-sensitive K⁺ channels and human eccrine sweat gland output

Abstract

The non‐selective NOS inhibitor L‐NAME has been shown to reduce cholinergic‐mediated sweating in humans. We tested the hypothesis that the effect of NOS inhibition on sweat gland out is mediated through the ability of NO to activate KCa1.1 channels. We generated stimulus response curves using: lactated‐Ringers, 50 mM TEA, 20 mM L‐NAME and a cocktail of 50 mM TEA plus 20 mM L‐NAME (n=10). Local sweat rate (SR) was measured by passing dry gas through a small sweat capsule mounted on the skin. The skin was stimulated at a constant current intensity of 2.5 mA for 30 s at frequencies of 0.2, 1, 2, 4, 6, 8, 12, 16, 32, and 64 Hz using two small stainless‐steel stimulating electrodes. We plotted the area under the SR‐time curve versus stimulus frequency. All data were expressed as the area under the local SR‐time curve (AUC) and normalize to the peak AUC response during Saline control trials (% AUC peak). During Ringers perfusion, peak local sweat output averaged 99.6 ± 5.7 AUC % peak which was significantly (p<0.0001) reduced by application of 50 mM TEA to 61.7 ± 22.7 AUC %peak. Addition of 20 mM L‐NAME to the 50 mM TEA solution produced an additional 20% reduction in peak SR to 42.5 ± 21.1 %AUC peak (p <0.05). These data support the hypothesis that sudomotor control of sweat gland activity is modulated by the presence of TEA sensitive K+ channels and the activity of an intrinsic NOS enzyme in the epithelial cells of the human sweat glands. Further, the ability of L‐NAME to produce an additional reduction in peak SR following 50 mM TEA indicates that the influence of NOS on local SR is not likely mediated via a modulation of TEA sensitive K+ channels. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The relative contribution of α‐ and β‐adrenergic sweating during heat exposure and the influence of sex and training status

“…In support of this possibility, long‐term heat acclimation has been shown to increase salivary glandular output in response to a given change in Ca 2+ signal in rats. [ 30 ] Intracellular elevation of Ca 2+ concentration stimulates Cl ‐ and K + channels to promote efflux of Cl ‐ and K + from sweat gland cell and ultimately promote sweat production [ 31‐34 ] that presumably relates to an increased cholinergic and α‐adrenergic sweating response in habitually trained men in the present study. Finally, our recent studies suggest the possibility that noradrenergic and/or β‐adrenergic but not α‐adrenergic mechanism would partly contribute to a high sweating response in endurance‐trained men during an exercise‐heat stress.…”

“…In support of this possibility, long-term heat acclimation has been shown to increase salivary glandular output in response to a given change in Ca 2+ signal in rats. [30] Intracellular elevation of Ca 2+ concentration stimulates Cland K + channels to promote efflux of Cland K + from sweat gland cell and ultimately promote sweat production [31][32][33][34] that presumably relates to an increased cholinergic and α-adrenergic sweating response in habitually trained men in the present study.…”

Role of nitric oxide synthase in human sweat gland output

“…Local sweating was activated by applying a mild (2.5 mA) intradermal electrical stimulation at a range of stimulus frequencies (0.2 to 64 Hz) (13,15). We used Seirin L-type #3 (0.2 ϫ 30 mm) stainless steel acupuncture needles as the stimulating electrodes.…”

“…The stimulator provided constant current delivery with a 300-s pulse, which was triggered by a square wave pulse from a Grass Model S48 stimulator. A 30-s stimulus duration provided sufficient discrimination between stimulus frequencies and allowed for a quantitative assessment of the sweating response (13,15).…”

“…Specifically, the NOS system within the clear cells of the human sweat gland may operate in a similar manner to vascular smooth muscle where nitric oxide directly opens K Ca 1.1 channels (1,2,10). Recent work has revealed that the nonselective selective K ϩ channel blocking agent tetraethylammonium chloride (TEA) reduced the local cholinergic sweating response by 30% (15). Here the follow-up study tested the hypothesis that L-NAME reduces local sweat rate by limiting K ϩ channel opening.…”