title: Preferential intracellular pH regulation: hypotheses and perspectives.
abstract: The regulation of vertebrate acid-base balance during acute episodes of elevated internal PCO2  is typically characterized by extracellular pH (pHe) regulation. Changes in pHe are associated with qualitatively similar changes in intracellular tissue pH (pHi) as the two are typically coupled, referred to as 'coupled pH regulation'. However, not all vertebrates rely on coupled pH regulation; instead, some preferentially regulate pHi against severe and maintained reductions in pHe Preferential pHi regulation has been identified in several adult fish species and an aquatic amphibian, but never in adult amniotes. Recently, common snapping turtles were observed to preferentially regulate pHi during development; the pattern of acid-base regulation in these species shifts from preferential pHi regulation in embryos to coupled pH regulation in adults. In this Commentary, we discuss the hypothesis that preferential pHi regulation may be a general strategy employed by vertebrate embryos in order to maintain acid-base homeostasis during severe acute acid-base disturbances. In adult vertebrates, the retention or loss of preferential pHi regulation may depend on selection pressures associated with the environment inhabited and/or the severity of acid-base regulatory challenges to which they are exposed. We also consider the idea that the retention of preferential pHi regulation into adulthood may have been a key event in vertebrate evolution, with implications for the invasion of freshwater habitats, the evolution of air breathing and the transition of vertebrates from water to land.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4 shartau@zoology.ubc.ca brauner@zoology.ubc.ca.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Shartau
authors.affiliation: Department of Fisheries and Aquaculture, Vancouver Island University, Nanaimo, British Columbia, Canada, V9R 5S5.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Baker
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton, TX 76203-5017, USA.
authors.forename: Dane A
authors.initials: DA
authors.lastname: Crossley
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4 shartau@zoology.ubc.ca brauner@zoology.ubc.ca.
authors.forename: Colin J
authors.identifier: 0000-0002-3695-7707
authors.initials: CJ
authors.lastname: Brauner
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D005075:Biological Evolution; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism*; D008954:Models, Biological; D014714:Vertebrates / Q000378:metabolism
keywords: Acid–base regulation; Amniotes; Development; Fish; Hypercarbia; Physiology; Preferential pHi regulation