pH regulation in hibernation: Implications for ventilatory and metabolic control

Mammals in hibernation retain a relatively constant blood plasma pH (extracellular pH; pH_e) that is typically alkaline relative to the pH of neutral water (pH_nw). Given that pH_nw increases as temperature falls, however, a constant pH_e in hibernation represents a reduction in the relative degree of alkalinity (i.e. a relative acidosis) of plasma and extracellular fluids. The manner in which this is achieved during entrance into, and arousal from hibernation, however, is not straightforward and has implications for the control of ventilation. Furthermore, intracellular pH (pH_i) changes in different ways in different tissues during hibernation. The dominant buffers involved in pH regulation are the imidazole buffer groups of histidyl residues of proteins and polypeptides. As a result, changes in the dissociation ratio of this buffer group (alpha imidazole; α_im) directly affect the net electric charge of all functional proteins. The pKa of the imidazole ring on histidine is close to pH_nw at 37 °C and increases with decreasing temperature with an almost identical slope to that seen for pH_nw. As a result, it has been suggested that the metabolic activity of tissues in which changes in pH_i parallel changes in pH_nw should be sustained while tissues in which changes in pH_i parallel changes in pH_e become relatively acidic and that this may contribute to metabolic suppression during hibernation. In this review we explore these implications.