pH Regulation in Glia and Neurons

Background

The pH change within the physiological range can act as a signal for transferring information to downstream substrates. However, in pathophysiologic conditions, a significant pH change can have a substantial influence on cell fate. Thus, the maintenance of pH homeostasis in the central nervous system (CNS) is of key importance for proper execution and regulation of neurotransmission, and deviations from this homeostasis are crucial in the mechanism underlying a spectrum of pathological conditions. In the CNS, changes in pH modulate events specific for its function: neuronal excitability, synaptic transmission, neurotransmitter uptake, and intercellular communication through gap junctions. It has also been suggested that pH gradients may be important in neuronal differentiation, growth cones, neurites, and pH in dendrite spines, learning, and memory. Therefore, the maintenance of adequate pH is a key factor in the functioning of the CNS.

Fig.1. pH regulation in the central nervous system. (Ruffin, 2014)

pH Transients in Both Glia and Neurons

The study of pH in the brain is distinguished by rapid increases or decreases in H⁺ that arise from electrical activity. pH transients can occur in three compartments of nervous tissues for neuronal stimulation to release neurotransmitters and hormones. These changes take place in time frames from milliseconds to minutes. These pH transients have possible modulatory roles, particularly in relation to membrane potential and excitability. The mechanisms that regulate these pH changes are of considerable neurobiological interest. Because of the pH dependence of various processes, pH transients may have a signaling character to solve the information processing in the nervous system.

Intracellular pH Regulation

Regulation of intracellular pH (pHi) can comprise the following processes: (1) cytosolic H⁺ buffering, (2) H⁺ sequestration into intracellular organelles, (3) release of metabolic production of H⁺, and (4) transmembrane movement of acid/base equivalents. Since the transport of acid equivalents and base equivalents must be driven against the H⁺/OH^- gradient in glial cells, they require some form of energy in most other cell types. These transport forms constitute the active pH regulation via membrane pumps and carriers. In addition, there may be H⁺ leak into the cytosol, either from intracellular organelles or from extracellular spaces.

Neuronal pH Homeostasis

The excitability of neurons is sensitive to changes in intracellular pH (pHi) and extracellular pH (pHo). Acid loading in neurons, a process that tends to lower pHi, predominantly results from the metabolic accumulation generated H⁺ and the extrusion of HCO3^- from cells via a Cl-HCO3 (anion) exchanger of the SLC4 solute carrier family. Acid extrusion is a process that tends to raise pHi. Conversely, acid-loading is a process that tends to restore steady-state pHi after an alkali load. Acid-extruding processes tend to restore steady-state pHi after an acid load.

pH Regulation in Glial

Glia controls the pH of the extracellular cerebrospinal fluid (CSF) that bathes neurons. Glial cells possess an array of mechanisms that modulate intaglio pH. Glial cells have been ascribed a special role in acid/base regulation in the brain, particularly the extracellular spaces. On the one hand, extracellular pH is influenced by the acid/base-coupled plasma membrane transporters, which are regulated by pH itself and by concentration gradients of other ions involved (often sodium) and by metabolites transported by these carrier systems. On the other hand, extracellular pH shifts are not necessarily be suppressed by active pH regulation but may be part of H⁺ signaling. Thus, acid/base-coupled transporters modulate each other when activated together.

Creative Biolabs offers customers over ten years of experience in applying a series of leading technologies and products for our customers worldwide. Please contact us to obtain excellence in services and products and to allow us to become a valuable partner of your team.

Reference

1. Ruffin, V. A.; et al. Intracellular pH regulation by acid-base transporters in mammalian neurons. Frontiers in physiology. 2014, 5, 43.