• amphibian epidermal surface fluid;
  • Cl/HCO3 exchange;
  • epithelial Cl channels;
  • mitochondria-rich cells;
  • patch clamp;
  • proton V-ATPase


In 1937, August Krogh discovered a powerful active Cl uptake mechanism in frog skin. After WWII, Hans Ussing continued the studies on the isolated skin and discovered the passive nature of the chloride uptake. The review concludes that the two modes of transport are associated with a minority cell type denoted as the γ-type mitochondria-rich (MR) cell, which is highly specialized for epithelial Cl uptake whether the frog is in the pond of low [NaCl] or the skin is isolated and studied by Ussing chamber technique. One type of apical Cl channels of the γ-MR cell is activated by binding of Cl to an external binding site and by membrane depolarization. This results in a tight coupling of the uptake of Na+ by principal cells and Cl by MR cells. Another type of Cl channels (probably CFTR) is involved in isotonic fluid uptake. It is suggested that the Cl channels serve passive uptake of Cl from the thin epidermal film of fluid produced by mucosal glands. The hypothesis is evaluated by discussing the turnover of water and ions of the epidermal surface fluid under terrestrial conditions. The apical Cl channels close when the electrodiffusion force is outwardly directed as it is when the animal is in the pond. With the passive fluxes eliminated, the Cl flux is governed by active transport and evidence is discussed that this is brought about by an exchange of cellular HCO3 with Cl of the outside bath driven by an apical H+ V-ATPase.