title: 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.
authors.affiliation: School of Applied Physiology, Georgia Institute of Technology, Atlanta, USA. brownmb@iupui.edu
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Brown
authors.forename: Karla K V
authors.initials: KK
authors.lastname: Haack
authors.forename: Brian P
authors.initials: BP
authors.lastname: Pollack
authors.forename: Mindy
authors.initials: M
authors.lastname: Millard-Stafford
authors.forename: Nael A
authors.initials: NA
authors.lastname: McCarty
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D051402:Aquaporin 5 / Q000378:metabolism; D001642:Bicycling; D001706:Biopsy; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D053503:Epithelial Sodium Channels / Q000378:metabolism; D015444:Exercise; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D009154:Mutation; D009481:Neurophysins / Q000097:blood; D010641:Phenotype; D011498:Protein Precursors / Q000097:blood; D012965:Sodium Chloride / Q000378:metabolism*; D013542:Sweat / Q000378:metabolism*; D013545:Sweat Glands / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013546:Sweating; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
chemical_list: C496036:AQP5 protein, human; C438657:AVP protein, human; D051402:Aquaporin 5; C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D009481:Neurophysins; D011498:Protein Precursors; D014667:Vasopressins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride; D000450:Aldosterone