Preferential intracellular pH regulation: hypotheses and perspectives

Abstract

The regulation of vertebrate acid-base balance during acute episodes of elevated internal P CO2 is typically characterized by extracellular pH ( pH e ) regulation. Changes in pH e are associated with qualitatively similar changes in intracellular tissue pH ( pH i ) 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 pH i against severe and maintained reductions in pH e . Preferential pH i 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 pH i during development; the pattern of acid-base regulation in these species shifts from preferential pH i regulation in embryos to coupled pH regulation in adults. In this Commentary, we discuss the hypothesis that preferential pH i 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 pH i 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 pH i 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.

Water pH limits extracellular but not intracellular pH compensation in the CO2 tolerant freshwater fish,Pangasianodon hypophthalmus

“…This elevated capacity for acute pH e compensation suggests that P. hypophthalmus might express pH coupled rather than pH pi to defend pH i in acute hypercarbia above 2 kPa P CO2 . This would be in stark contrast to findings for 19 of 20 CO 2 -tolerant freshwater fishes tested (Shartau et al, 2016), including the Amazonian catfish Pterygoplichthys pardalis, which expresses pH pi and negligible pH e compensation at 1-6 kPa P CO2 (Brauner et al, 2004). However, pH i in P. hypophthalmus was not examined for preferential regulation, and water pH during hypercarbic exposure was 5.8 (Damsgaard et al, 2015).…”

“…2), and did not recover within 20 h despite significantly increasing in pH 4.5 water. Lack of RBC pH i regulation has been observed in all fishes expressing pH pi to date (Shartau et al, 2016) and is consistent with the absence of β-adrenergically stimulated Na + −H + exchange in Siluriformes (Berenbrink et al, 2005;Phuong et al, 2017). Despite this variation, the observed patterns in pH i across all tissues in both treatments were typical of pH pi expression (Shartau et al, 2016), and are corroborated by the reduction in plasma [HCO 3 − ] below the blood buffer line observed after 3 h of hypercarbia in both treatments.…”

“…Coupled pH regulation (pH coupled ) and preferential intracellular pH regulation (pH pi ) are two strategies fish use to compensate for an acute respiratory acidosis (Shartau et al, 2016). These strategies represent endpoints of a continuum along which rates and degrees of intracellular pH (pH i ) and extracellular pH (pH e ) compensation vary.…”

“…Why fishes express pH coupled or pH pi is unclear. However, severe acute hypercarbia is hypothesized to select for pH pi by exceeding the capacity and/or limiting the rate of acute pH e compensation required for pH coupled to defend pH i (Shartau et al, 2016). Indeed, full pH e compensation within 24-48 h of hypercarbia is limited to ∼2 kPa P CO2 in most freshwater fishes tested, while many fishes expressing pH pi can robustly defend pH i above 6 kPa P CO2 without pH e compensation (Brauner and Baker, 2009;Shartau et al, 2016).…”

“…However, severe acute hypercarbia is hypothesized to select for pH pi by exceeding the capacity and/or limiting the rate of acute pH e compensation required for pH coupled to defend pH i (Shartau et al, 2016). Indeed, full pH e compensation within 24-48 h of hypercarbia is limited to ∼2 kPa P CO2 in most freshwater fishes tested, while many fishes expressing pH pi can robustly defend pH i above 6 kPa P CO2 without pH e compensation (Brauner and Baker, 2009;Shartau et al, 2016). One hypothesis for this apparent limit to acute pH e compensation suggests many fishes are unable to elevate plasma bicarbonate above the ∼25-30 mmol l −1 required for full pH e recovery at ∼2 kPa P CO2 , let alone the ∼100-150 mmol l −1 required at ∼6 kPa (Heisler, 1984;Brauner and Baker, 2009).…”