Interaction between ammonia excretion and ion regulation

Ammonia is the primitive nitrogenous end product of protein metabolism. Most bony fish are ammonotelic, meaning they excrete toxic ammonia mostly from their gills and integument. When ammonia gas (NH3) diffuses out of the gill epithelia, it reacts with H+ to form ionic NH4+. This acid-trapping process maintains a favorable gradient for NH3 diffusion. Transmembrane channel proteins such as Rhesus glycoproteins are known to facilitate NH3 diffusion across cell membranes. Ionocytes in the gill epithelia of freshwater fish are responsible for ion (Na+, Cl−, and Ca2+) uptake, and a specific subtype of ionocyte is known to conduct NH4+-dependent Na+ uptake (or Na+/NH4+ exchange; i.e., a linkage between ammonia excretion and ion regulation). The Rhesus glycoprotein, H+-ATPase, and Na+/H+ exchanger in the apical membrane of ionocytes are the major players in the mechanism. In the basolateral membrane of ionocytes, Na+/K+-ATPase and Na+/K+/2Cl− cotransporter may play a critical role in the active transport of NH4+. With this mechanism, ionocytes can take up Na+ from very dilute environments and secrete NH4+ against concentration gradients.