Low abundance of sweat duct Cl⁻channel CFTR in both healthy and cystic fibrosis athletes with exceptionally salty sweat during exercise

Abstract

To understand potential mechanisms explaining interindividual variability observed in human sweat sodium concentration ([Na(+)]), we investigated the relationship among [Na(+)] of thermoregulatory sweat, plasma membrane expression of Na(+) and Cl(-) transport proteins in biopsied human eccrine sweat ducts, and basal levels of vasopressin (AVP) and aldosterone. Lower ductal luminal membrane expression of the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR) was observed in immunofluorescent staining of sweat glands from healthy young adults identified as exceptionally "salty sweaters" (SS) (n = 6, P < 0.05) and from patients with cystic fibrosis (CF) (n = 6, P < 0.005) compared with ducts from healthy young adults with "typical" sweat [Na(+)] (control, n = 6). Genetic testing of healthy subjects did not reveal any heterozygotes ("carriers") for any of the 39 most common disease-causing CFTR mutations in the United States. SS had higher baseline plasma [AVP] compared with control (P = 0.029). Immunostaining to investigate a potential relationship between higher plasma [AVP] (and sweat [Na(+)]) and ductal membrane aquaporin-5 revealed for all groups a relatively sparse and location-dependent ductal expression of the water channel with localization primarily to the secretory coil. Availability of CFTR for NaCl transport across the ductal membrane appears related to the significant physiological variability observed in sweat salt concentration in apparently healthy humans. At present, a heritable link between healthy salty sweaters and the most prevalent disease-causing CFTR mutations cannot be established.

Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise

“…AQP5 water channels have been identified within the apical membrane of secretory cells located in salivary, sweat, lacrimal, and airway submucosal glands as well as in corneal, nasopharyngeal, bronchial, and uterus epithelium (4,20,28,43). AQP5 channels in sweat duct epithelium have been found in the distal apical tubule segments (4), a location mirroring that of the collecting duct principle cells within the kidney (17).…”

Three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes transdifferentiation of BM-MSCs

“…The functional proteins play important roles in sweat secretion and absorption (Brown et al 2011;Granger et al 2003;Nejsum et al 2005;Reddy and Quinton 2003). In our studies, cellular polarization is reflected by the expression of cell junction proteins, ZO-2, E-cadherin and desmoglein-2, and the functional proteins Na ?…”

Особливості Діагностики Та Лікування Гіпонатріємії В Дітей

“…При муковисцидозе потеря натрия обусловлена наруше-нием транспорта натрия в выводных протоках по-товых желез (синдром псевдо-Барттера) [12]. Реже гипонатриемия развивается при обширных ожогах с нарушением естественной барьерной функции кожи [13]. Научный обзор / Scientific Review пространстве, где не действуют физиологические механизмы регуляции.…”