Recent evidence suggests that
carbonic anhydrase (CA) IX in humans is under the regulatory control of
hypoxia-inducible factor and is overexpressed in certain
cancers. However, little is known of its presence in nonmammalian vertebrates or its physiological function in any vertebrate. The objective of this study was to examine and characterize the presence, distribution, induction by
hypoxia, and physiological function of CA IX in the zebrafish. Zebrafish CA IX was highly expressed in the eye, brain, and gastrointestinal tract and showed increased expression in the eye, brain, and muscle in response to
hypoxia (water Po(2) = 24 mmHg). The hypothesis that increased CA IX expression during
hypoxia would act to attenuate intracellular
acidosis was then examined. Muscle intracellular pH (pH(i)) decreased after 4 h of hypoxic exposure (from 7.15 +/- 0.02 to 7.06 +/- 0.01 pH units) and did not recover by 24 h. Manipulation of extracellular CA activity via
intraperitoneal injection of either bovine CA or the selective extracellular CA inhibitor
F3500 revealed that although increased CA activity could fully restore pH(i), removal of extracellular activity did not result in further
acidosis. An exercise-induced
acidosis was also attenuated in fish treated with bovine CA; however, the increased extracellular CA expression resulting from
hypoxia had no affect. These data suggest that although extracellular CA can potentially minimize the impact of
hypoxia on muscle pH(i), the actual level of extracellular CA activity is likely insufficient to achieve this goal, even when enhanced by
hypoxia-induced increases in CA IX expression.