Sodium/Hydrogen Exchanger (Solute Carrier Family 9)

The sodium/hydrogen exchangers (NHE) are among the main regulators of cell volume and intracellular concentration of hydrogen and sodium ions. They transport sodium out of the cell, and hydrogen into the cell. They are expressed on the membranes of many cells, especially those in the nephron of the kidney. These transporter proteins play an important role in intracellular pH and cell volume regulation, cell growth, and differentiation, stimulus-response coupling with white cells and platelets, the metabolic response to hormones like insulin and glucocorticoids, and the transepithelial absorption and secretion of sodium, hydrogen, bicarbonate and chloride ions, and organic anions. Alteration in the function of NHEs may lead to diverse human diseases such as kidney failure, cardiovascular diseases, cancer, and many brain diseases like epilepsy, Alzheimer's disease, neuropathic pain and ischemia/reperfusion-induced cerebral injury. Clinically, inhibitors of these transporters that prevent myocardial infarction and other heart diseases like congestive heart failure have been developed. Moreover, in preclinical animal models NHE inhibitors (e.g., amiloride and cariporide) produce protective effects on ischemia/reperfusion-induced brain injury (e.g., stroke), exhibit good antiepileptic potential and attenuate neuropathic pain.

Here, we present an introduction of the following human NHE transporter proteins concerning the substrate specificity, regulation, physiological roles, and pathophysiological roles. Some of these proteins are less well-characterized and their mechanisms and functions remain to be further investigated using more advanced techniques.

Human Sodium/Hydrogen Exchanger Family Members

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