Role of Cholinergic Agonists & Hyperthermia on Regional Skin Barriers: Exposure Science Implications
Faculty Mentor Information
Dr. Thad Wilson (Mentor), University of Kentucky
Abstract
The skin impedes entry to harmful exposures, and neural-induced changes to skin condition or function may impact barrier stability. In this study, we explored how cholinergic neurotransmitters influence skin barriers by assessing epithelial transport. We hypothesized increasing methylcholine (MCh) or acetylcholine (ACh) would decrease transepithelial resistance across mouse pawpad skin at skin (32°C) or internal (37°C) temperature. We also predicted transepithelial resistance would be higher in tail skin vs pawpads, and subjecting samples to 40°C (heat stress) would lower transepithelial resistance compared to 32°C.
30 C57BL/6 mouse rear pawpads (containing sweat glands) and seven mouse tail skins (no sweat glands) were dissected and mounted into a vertical Ussing chamber filled with Krebs bicarbonate buffer, gassed with 95% O2/5% CO2, and encased in a temperature jacket. Transepithelial resistance utilized a current clamp and was measured using Ag–AgCl2 electrodes placed in both epidermal and hypodermal baths with hypodermal-side-only cholinergic dosing.
MCh and ACh (data not shown) invoked significant dose-dependent decreases in transepithelial resistance in pawpads at 37°C and 32 °C. Tail skin transepithelial resistance was higher than pawpad skin, and MCh decreased transepithelial resistance significantly at both sites. Increasing temperature to 40°C altered the magnitude of decrease in transepithelial resistance to MCh in pawpads compared to 32°C. Increased ion movement (signifying a leakier epithelium) occurred with cholinergic stimulation and local hyperthermia, suggesting neural and external influences can sufficiently affect skin function enough to alter regional skin barriers.
Role of Cholinergic Agonists & Hyperthermia on Regional Skin Barriers: Exposure Science Implications
The skin impedes entry to harmful exposures, and neural-induced changes to skin condition or function may impact barrier stability. In this study, we explored how cholinergic neurotransmitters influence skin barriers by assessing epithelial transport. We hypothesized increasing methylcholine (MCh) or acetylcholine (ACh) would decrease transepithelial resistance across mouse pawpad skin at skin (32°C) or internal (37°C) temperature. We also predicted transepithelial resistance would be higher in tail skin vs pawpads, and subjecting samples to 40°C (heat stress) would lower transepithelial resistance compared to 32°C.
30 C57BL/6 mouse rear pawpads (containing sweat glands) and seven mouse tail skins (no sweat glands) were dissected and mounted into a vertical Ussing chamber filled with Krebs bicarbonate buffer, gassed with 95% O2/5% CO2, and encased in a temperature jacket. Transepithelial resistance utilized a current clamp and was measured using Ag–AgCl2 electrodes placed in both epidermal and hypodermal baths with hypodermal-side-only cholinergic dosing.
MCh and ACh (data not shown) invoked significant dose-dependent decreases in transepithelial resistance in pawpads at 37°C and 32 °C. Tail skin transepithelial resistance was higher than pawpad skin, and MCh decreased transepithelial resistance significantly at both sites. Increasing temperature to 40°C altered the magnitude of decrease in transepithelial resistance to MCh in pawpads compared to 32°C. Increased ion movement (signifying a leakier epithelium) occurred with cholinergic stimulation and local hyperthermia, suggesting neural and external influences can sufficiently affect skin function enough to alter regional skin barriers.