The physiology of fish at low pH: the zebrafish as a model system.

Ionic regulation and acid-base balance are fundamental to the physiology of vertebrates including fish. Acidification of freshwater ecosystems is recognized as a global environmental problem, and the physiological responses to acid exposure in a few fish species are well characterized. However, the underlying mechanisms promoting ionic and acid-base balance for most fish species that have been investigated remain unclear. Zebrafish (Danio rerio) has emerged as a powerful model system to elucidate the molecular basis of ionic and acid-base regulation. The utility of zebrafish is related to the ease with which it can be genetically manipulated, its suitability for state-of-the-art molecular and cellular approaches, and its tolerance to diverse environmental conditions. Recent studies have identified several key regulatory mechanisms enabling acclimation of zebrafish to acidic environments, including activation of the sodium/hydrogen exchanger (NHE) and H(+)-ATPase for acid secretion and Na(+) uptake, cortisol-mediated regulation of transcellular and paracellular Na(+) movements, and ionocyte proliferation controlled by specific cell-fate transcription factors. These integrated physiological responses ultimately contribute to ionic and acid-base homeostasis in zebrafish exposed to acidic water. In the present review, we provide an overview of the general effects of acid exposure on freshwater fish, the adaptive mechanisms promoting extreme acid tolerance in fishes native to acidic environments, and the mechanisms regulating ionic and acid-base balance during acid exposure in zebrafish.