Baker DW, Matey V, Huynh KT, Wilson JM, Morgan JD, Brauner CJ. Complete intracellular pH protection during extracellular pH depression is associated with hypercarbia tolerance in white sturgeon, Acipenser transmontanus. Am J Physiol Regul Integr Comp Physiol 296: R1868 -R1880, 2009. First published April 1, 2009 doi:10.1152/ajpregu.90767.2008.-Sturgeons are among the most CO 2 tolerant of fishes investigated to date. However, the basis of this exceptional CO 2 tolerance is unknown. Here, white sturgeon, Acipenser transmontanus, were exposed to elevated CO 2 to investigate the mechanisms associated with short-term hypercarbia tolerance. During exposure to 1.5 kPa PCO 2, transient blood pH [extracellular pH (pHe)] depression was compensated within 24 h and associated with net plasma HCO 3 Ϫ accumulation and equimolar Cl Ϫ loss, and changes in gill morphology, such as a decrease in apical surface area of mitochondrial-rich cells. These findings indicate that pHe recovery at this level of hypercarbia is accomplished in a manner similar to most freshwater teleost species studied to date, although branchial mechanisms involved may differ. White sturgeon exposed to more severe hypercarbia (3 and 6 kPa PCO 2) for 48 h exhibited incomplete pH compensation in blood and red blood cells. Despite pHe depression, intracellular pH (pHi) of white muscle, heart, brain, and liver did not decrease during a transient (6 h of 1.5 kPa PCO 2 ) or prolonged (48 h at 3 and 6 kPa PCO 2) blood acidosis. This pHi protection was not due to high intrinsic buffering in tissues. Such tight active cellular regulation of pHi in the absence of pHe compensation represents a unique pattern for non-air-breathing fishes, and we hypothesize that it is the basis for the exceptional CO 2 tolerance of white sturgeon and, likely, other CO 2 tolerant fishes. Further research to elucidate the specific mechanisms responsible for this tremendous pH regulatory capacity in tissues of white sturgeon is warranted. sturgeon; acid-base regulation; intracellular pH; CO 2 tolerance; hypercarbia/hypercapnia AQUATIC HYPERCARBIA (elevated PCO 2 in water) occurs in fresh and estuarine systems, and Pw CO 2 levels as great as 8 kPa (20-to 30-fold increase over the resting arterial Pa CO 2 of fish) have been observed (24,55) (16)] changes at the gill. These changes in branchial morphology and acid-base-relevant ion transporters may aid with the net acid secretion or base absorption mechanisms necessary to promote blood pH compensation (16,20), although direct evidence for this is lacking.Changes in intracellular pH (pHi) in most fish species studied to date are qualitatively similar to, albeit smaller than, blood pH changes during a respiratory acidosis (6, 49). Because function of many cellular components, such as enzyme activity, is pH sensitive, a general acidosis may have severe consequences on cellular processes, including metabolic energy production (25, 50). Only a handful of studies have measured pHi and pHe simultaneously during hypercarbia in fish; these studies...