Freshwater Fish Gill Ion Transport: August Krogh to morpholinos and microprobes

August Krogh proposed that freshwater fishes (and other freshwater animals) maintain body NaCl homoeostasis by extracting these ions from the environment via separate Na+/NH4+ and Cl−/HCO3− exchangers in the gill epithelium. Subsequent data from other laboratories suggested that Na+ uptake was more probably coupled to H+ secretion via a vesicular proton pump (V‐ATPase) electrically coupled to a Na+ channel. However, despite uncertainty about electrochemical gradients, evidence has accrued that epithelial Na+/H+ exchange indeed may be an alternative pathway for Na+ uptake. The specific pathways for Na+ uptake may be species and environment specific. An apical Cl−/HCO3− exchanger is generally accepted for most species (some species do not extract Cl− from freshwater), but the relative roles of anion exchanger‐like (SLC4A1) vs. pendrin‐like (SLC26Z4) exchangers are unknown, and also may be species specific. Most recently, data have supported the presence of an apical Na+ + Cl− cotransporter (NCC‐type), despite thermodynamic uncertainty. Ammonia extrusion may be via NH3 diffusing through the paracellular junctions or NH4+ substitution on both basolateral and apical ionic exchangers (Na+ + K+‐ATPase; Na+ + K+ + Cl− ‐ cotransporter; and Na+/H+ exchanger), but recent evidence suggests that Rhesus‐glycoproteins mediate both basolateral and apical movement of ammonia.