Salt-secreting ionocytes in marine fishes: new dimensions and evolutionary implications of a fundamental model

To reside in marine habitats, marine fishes must actively eliminate the excess Na+ and Cl- they acquire from their environment. These ions are passively absorbed across body surfaces and through the ingestion of seawater (SW), which is necessary to maintain water balance. Salt secretion occurs through the actions of mitochondrion-rich 'SW-type ionocytes' in the gills or other specialized salt-secreting organs. For nearly 50 years, the SW-type ionocyte model proposed by Patricio Silva and colleagues has proven remarkably enduring. The Silva model guided researchers toward identifying key molecular components of SW-type ionocytes, such as cystic fibrosis transmembrane conductance regulator 1 (Cftr1), Na+/K+/2Cl- cotransporter 1 (Nkcc1) and the inwardly rectifying K+ channel (Kir). However, emerging findings indicate that alternative molecular mechanisms may complement, or in some cases, operate in lieu of those included in the Silva model. In this Commentary, we argue that it is time to critically evaluate whether ionocyte-based strategies for salt secretion are more diverse than currently recognized. We highlight recent developments regarding the operation of Cftr-independent ionocytes in lamprey, the emerging role of anoctamin 1 (Ano1) in lamprey and bony fishes, and various 'new' pathways for Cl- and K+ to enter and exit ionocytes. Additionally, we propose future research directions for identifying novel salt-secretory mechanisms in various lineages of marine fishes. We conclude this Commentary by presenting three hypotheses for the divergence of ionocyte-mediated salt secretion in marine fishes and outlining a conceptual framework for considering the evolutionary homology of salt-secreting ionocytes across vertebrates.