The role of Na+/H+ exchangers (NHEs) in pH regulation and brain function

The regulation of pH (a measure of acidity or alkalinity) is a highly sophisticated and tightly controlled process that is extremely important for proper brain function. Abnormal fluctuations in the pH of neurons (nerve cells) may be involved in the development of many neurological disorders such as epilepsy. Sodium-proton exchangers (NHEs) are membrane proteins that play an important role in maintaining and regulating cellular pH. Two forms of these proteins in humans, NHE1 and NHE5, are found at high levels in the brain. Graham Diering is investigating the exact function of NHE5, the only NHE that occurs almost exclusively and at high levels in the brain. NHE5 has been linked to familial paroxysmal kinesigenic dyskinesia (PKD), a neurological movement disorder. However, the precise involvement of the protein in PKD, and its role in proper brain function, are unknown. Diering is researching NHE5 in different brain structures, including mature and developing tissue, and examining the protein at the cellular level to determine where it may be active in nerve cells. An enhanced knowledge of the mechanisms in nerve cells that regulate pH could increase understanding of the factors that govern brain function, both in the normal and diseased state. As well, an analysis of specific molecules involved in this process could contribute to development of diagnostic and therapeutic strategies for treatment of neurological disorders.