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

Abstract

The transepithelial electrical potential difference (Vt) and the transepithelial resistance (Rt) 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 Vt and Rt were -10.7 +/- 1.1 (mV, lumen negative) and 10.9 +/- 1.7 (omega X cm2). Bilateral substitution of Cl- by gluconate increased Vt and Rt to -42.7 +/- 5.1 (mV) and 98.0 +/- 12.0 (omega X cm2), respectively. Luminal application of amiloride (10(-4) mol/l) collapsed Vt and increased Rt to 11.4 +/- 1.7 and 159.7 +/- 12.0 omega X 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 Vt and Rt were high already in Cl- Ringer solution (-78.9 +/- 9.9 mV and 91.2 +/- 15.6 omega X 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 conformation of what has been postulated previously from simple potential measurements.