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 Rhesusglycoproteins mediate both basolateral and apical movement of ammonia.