Na+ K+ ATPase isoform switching in zebrafish during transition to dilute freshwater habitats.

Na+ K+ ATPase (NKA) is crucial to branchial ion transport as it uses the energy from ATP to move Na+ against its electrochemical gradient. When fish encounter extremely dilute environments the energy available from ATP hydrolysis may not be sufficient to overcome thermodynamic constraints on ion transport. Yet many fish species-including zebrafish-are capable of surviving in dilute environments. Despite much study, the physiological mechanisms by which this occurs remain poorly understood. Here, we demonstrate that zebrafish acclimated to less than 10 µM Na+ water exhibit upregulation of a specific NKA α subunit ( zatp1a1a.5) that, unlike most NKA heterotrimers, would result in transfer of only a single Na+ and K+ per ATP hydrolysis reaction. Thermodynamic models demonstrate that this change is sufficient to reduce the activation energy of NKA, allowing it to overcome the adverse electrochemical gradient imposed by dilute freshwater. Importantly, upregulation of zatp1a1a.5 also coincides with the recovery of whole body Na+ post-transfer, which occurs within 24 h. While these structural modifications are crucial for allowing zebrafish to survive in ion-poor environments, phylogenetic and structural analysis of available α subunits from a range of teleosts suggests this adaptation is not widely distributed.