Teleostean fishes may have developed an efficient Na+ uptake for adaptation to the freshwater system

Abstract

Understanding Na+ uptake mechanisms in vertebrates has been a research priority since vertebrate ancestors were thought to originate from hyperosmotic marine habitats to the hypoosmotic freshwater system. Given the evolutionary success of osmoregulator teleosts, these freshwater conquerors from the marine habitats are reasonably considered to develop the traits of absorbing Na+ from the Na+-poor circumstances for ionic homeostasis. However, in teleosts, the loss of epithelial Na+ channel (ENaC) has long been a mystery and an issue under debate in the evolution of vertebrates. In this study, we evaluate the idea that energetic efficiency in teleosts may have been improved by selection for ENaC loss and an evolved energy-saving alternative, the Na+/H+ exchangers (NHE3)-mediated Na+ uptake/NH4+ excretion machinery. The present study approaches this question from the lamprey, a pioneer invader of freshwater habitats, initially developed ENaC-mediated Na+ uptake driven by energy-consuming apical H+-ATPase (VHA) in the gills, similar to amphibian skin and external gills. Later, teleosts may have intensified ammonotelism to generate larger NH4+ outward gradients that facilitate NHE3-mediated Na+ uptake against an unfavorable Na+ gradient in freshwater without consuming additional ATP. Therefore, this study provides a fresh starting point for expanding our understanding of vertebrate ion regulation and environmental adaptation within the framework of the energy constraint concept.

Molecular Physiological Evidence for the Role of Na+-Cl− Co-Transporter in Branchial Na+ Uptake in Freshwater Teleosts

“…In order to lower the final loss of Na + in the urine and keep the blood Na + concentration within a normal physiological range, mammals fed a low-Na + diet would decrease their glomerular filtration rate (GFR) and increase Na + reabsorption of the nephrons by upregulating the expression of renal Ncc and epithelial Na + channel (Enac), but not necessarily Nhe3 [ 38 , 39 ]. Notably, in teleosts (lacking Enac genes [ 40 ]), a long-term exposure to low-Na + FW would trigger both Ncc and Nhe3, and thereby enhance Na + uptake capacity ( Figure 3 , Figure 4 and Figure 5 ) [ 30 , 31 , 32 , 41 , 42 ]. In fact, it is reasonable to observe compensatory mechanisms of discrepancy between mammals and teleosts in the regulation of Nhe3 and Ncc.…”

“…In fact, it is reasonable to observe compensatory mechanisms of discrepancy between mammals and teleosts in the regulation of Nhe3 and Ncc. Functionally similar but facing different external media, mammalian renal epithelial cells are located in the lining of the lumen with a high osmolarity fluid ([Na + ] = 25–350 mM [ 43 , 44 ]), but teleost ionocytes are exposed to hypotonic FW ([Na + ] < 1 mM [ 9 , 41 ]). In addition, filtered Na + from the glomeruli is sequentially absorbed along the tubule of nephrons, first by Nhe3 and then by Ncc and Enac [ 45 ].…”

“…The distal convoluted tubule (DCT, where the Ncc expresses) and collecting duct (CD, where the Enac expresses) account for less than 10% of the total Na + reabsorption [ 45 ]. In teleosts, electrophysiological and pharmacological studies in the larval skin suggest that around 70% and 75% of Na + is taken up by Nhe in medaka and in low-Na + -acclimated zebrafish, respectively [ 30 , 41 ]. Adult zebrafish treated with EIPA (Nhe inhibitor) also showed an over 50% decline in whole-body Na + influx (according to measurements made with a radiotracer) [ 7 ].…”

“…These findings and the comparisons between mammals and teleosts raise the question of why teleosts tend to utilize Nhe (instead of Ncc) as the major transporter for Na + uptake even though the environmental conditions and the cell distribution are totally different from those in mammalian kidneys. A possible reason is that ionocytes contain a higher intracellular [NH 4 + ] than FW [ 9 , 41 ]. Because Nhe exhibits not only Na + /H + but Na + /NH 4 + exchange activities, teleost ionocytes most likely rely on a favorable outward NH 4 + gradient to efficiently drive Nhe and simultaneously take up Na + from hypotonic FW [ 9 , 10 , 41 , 50 ].…”

“…A possible reason is that ionocytes contain a higher intracellular [NH 4 + ] than FW [ 9 , 41 ]. Because Nhe exhibits not only Na + /H + but Na + /NH 4 + exchange activities, teleost ionocytes most likely rely on a favorable outward NH 4 + gradient to efficiently drive Nhe and simultaneously take up Na + from hypotonic FW [ 9 , 10 , 41 , 50 ]. However, the electrical/chemical gradients generated by basolateral Nka seem to be ineffective in driving ionocyte Ncc against unfavorable Na + /Cl − gradients [ 3 , 9 ].…”