Na⁺/H⁺ Exchange in Mammalian Digestive Tract

The Slc9a family of Na+/H+ exchangers (NHEs) plays a critical role in neutral sodium absorption in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins mediate the electroneutral exchange of Na+ and H+ and are crucial in a variety of physiological processes, including the transepithelial Na+ and water absorption, fine tuning of intracellular pH, cell volume control and systemic electrolyte, and acid-base and fluid volume homeostasis. They also secondarily affect other cellular transport mechanisms as well as cell survival, motility, adhesion, and repair mechanisms. In this chapter, we review the role of the Na+/H+ exchange mechanism as it relates to the physiology of organs and cells involved in nutrient intake and absorption, and we describe physiological and molecular aspects of individual isoforms, including their structure, tissue-, and subcellular distribution, as well as their regulation by physiological stimuli at the transcriptional and posttranscriptional levels. Consequences of gene-targeted mutation of individual isoforms are discussed in the context of the physiology of digestive organs. Where available, we also provide a review of pathophysiological states related to aberrant expression and/or activity of NHEs within the confines of the digestive system.