Direct demonstration of high transepithelial chloride-conductance in normal human sweat duct which is absent in cystic fibrosis

Abstract

The transepithelial electrical potential difference (V_t) and the transepithelial resistance (R_t) were measured across individual microdissected sweat ducts obtained from biopsies of the scapular region of normal human volunteers and of a Cystic Fibrosis (CF) patient. During luminal and contraluminal perfusion with NaCl Ringer solution V_t and R_t were −10.7±1.1 (mV, lumen negative) and 10.9±1.7 (Ω·cm²). Bilateral substitution of Cl⁻ by gluconate increased V_t and R_t to −42.7±5.1 (mV) and 98.0±12.0 (Ω·cm²), respectivley. Luminal application of amiloride (10⁻⁴ mol/l) collapsed V_t and increased R_t to 11.4±1.7 and 159.7±12.0 Ω·cm² in Cl⁻ and gluconate Ringer respectively. These data indicate that 90% of the total transepithelial conductance is attributed to Cl⁻ and 5% to Na⁺ while the remaining 5% is unaccounted for at present. In CF ducts V_t and R_t were high already in Cl⁻ Ringer solution (−78.9±9.9 mV and 91.2±15.6 Ω·cm²) and did not change significantly after replacement of Cl⁻ by gluconate. The data demonstrate that normal human sweat duct epithelium, despite its ability to generate high electric and osmotic gradients, is a low resistance epithelium, probably because of a high Cl⁻-permeability of its cell membranes. In addition, the data demonstrate that this Cl⁻-conductance is missing in CF, in confirmation of what has been postulated previously from simple potential measurements.