Acid-base transport and pH regulation

Abstract

In the brain, neurons and glial cells are equipped with a number of acid-base-coupled ion and metabolite transporters, which affect intra- and extracellular pH. The pH changes can be fast and multiphasic, which can be considered as H+ signaling in cells and tissues. Since many biological processes, such as metabolic activity, synaptic transmission, and electrical excitability, as well as most enzymatic processes in the cells, are dependent on and/or modulated by H+, changes in pH may be involved in shaping intra- and intercellular signaling patterns. The ubiquitous enzyme carbonic anhydrase (CA), which helps to modify the kinetics of pH changes, may increase the buffering capacity in cells or cellular compartments, and can enhance the activity of some acid-base transporters by binding and forming transport metabolons with these proteins. Some acid-base transporters, such as the Na+/H+ exchanger (NHE), the Cl-/exchanger (anion exchanger, AE), or the Na+/ cotransporter (NBC), are more directly involved in the regulation of intra- and extracellular pH, while other transporters, which primarily transport, e.g., neurotransmitters (glutamate), neurotransmitter precursors (glutamine), or energetic compounds (lactate), co- or countertransport H+ as cosubstrate across the cell membrane, and are therefore affected by the H+ gradient. Protons gate acid-sensing ion channels (ASICs) involved in the perception of pain, touch, and heat. Pathological pH changes are associated with hypoxia and ischemia and subsequent lactacidosis. Hence, changes of pH in the nervous system, as affected by intra- and extracellular H+ buffering capacity, metabolically released acids, and the activity of acid-base transporters in cell membranes, modulate neuronal activity and glial functions. © 2007 Springer Science+Business Media, LLC.