UC San Diego

White seabass (Atractoscion nobilis) increasingly experience periods of low oxygen (O₂; hypoxia) and high carbon dioxide (CO₂, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O₂ carrier in the blood and in many teleost fishes Hb-O₂ binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically stimulated sodium-proton-exchangers (β-NHEs). We hypothesized that RBC β-NHEs in white seabass are an important mechanism that can protect the blood O₂-carrying capacity during hypoxia and hypercapnia. We determined the O₂-binding characteristics of white seabass blood, the cellular and subcellular response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O₂ saturation. White seabass had typical teleost Hb characteristics, with a moderate O₂ affinity (Po₂ at half-saturation; P₅₀ 2.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed β-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results and a functional characterization of β-NHE activity. The activation of RBC β-NHEs increased Hb-O₂ saturation by ∼8% in normoxic hypercapnia and by up to ∼20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. β-NHE activity in white seabass has great potential to protect arterial O₂ transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.