AUTHOR=Ruffin Vernon A., Salameh Ahlam I., Boron Walter F., Parker Mark D.

TITLE=Intracellular pH regulation by acid-base transporters in mammalian neurons

JOURNAL=Frontiers in Physiology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00043

DOI=10.3389/fphys.2014.00043

ISSN=1664-042X

ABSTRACT=<p>Intracellular pH (pH<sub>i</sub>) regulation in the brain is important in both physiological and physiopathological conditions because changes in pH<sub>i</sub> generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pH<sub>i</sub> on cellular processes in the brain, including channel activity and neuronal excitability. (2) pH<sub>i</sub> homeostasis and how it is determined by the balance between rates of acid loading (<italic>J</italic><sub>L</sub>) and extrusion (<italic>J</italic><sub>E</sub>). The balance between <italic>J</italic><sub>E</sub> and <italic>J</italic><sub>L</sub> determine steady-state pH<sub>i</sub>, as well as the ability of the cell to defend pH<sub>i</sub> in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to <italic>J</italic><sub>L</sub> (namely the Cl-HCO<sub>3</sub> exchanger AE3) and <italic>J</italic><sub>E</sub> (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na<sup>+</sup>- coupled HCO<sub>3</sub><sup>−</sup> transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pH<sub>i</sub> under physiopathologic conditions.</p>