Mechanisms and functional role of intracellular pH regulation in hepatocytes.

Intracellular pH influences and is influenced by a diverse array of hepatocellular processes. It is regulated by the concerted action of three plasma membrane H+/HCO3- transporters that serve to buffer against both acidic (Na+/H+ exchange, Na+/HCO3- cotransport) and basic (Cl-/HCO3- exchange) metabolic challenges. The responsiveness of hepatocytes to these challenges is augmented by a regulatory interplay between pH-mediated changes in Vm and electrogenic Na+/HCO3- cotransport to maintain pHi and Vm within a range optimized to serve liver function. The cost is expenditure of metabolic energy to sustain increased activity of the Na+/K+ pump. The benefit is a dynamic servomechanism well-suited to the metabolic demands of hepatocytes, which may be found in future studies to be employed in other metabolically active epithelia as well.