All living cells are critically dependent on homeostatic mechanisms that regulate intracellular pH, Na+ content, and, as a result, cell volume. Correspondingly, Na+ and H+ are among the most prevalent ions in living cells and are essential in cell bioenergetics. In 1974, West and Mitchell discovered sodium proton antiport activity in bacterial cells and suggested that Na+/H+ antiporter proteins have primary roles in the homeostasis of these cations (West and Mitchell 1974). Since then, sodium proton antiporters have been identified in the cytoplasmic and organelle membranes of almost all cells, including those of plants, animals and microorganisms. Furthermore, increasing numbers of these antiporters are being identified as human drug targets.
The SLC9 gene family encodes Na+/H+exchangers (NHEs) in many species from prokaryotes to eukaryotes. In humans, these proteins are associated with the...
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