Apical NAplus-Hplus exchangers in the mammalian gastrointestinal tract
The Slc9a family of nine Na+/H+ exchangers (NHE) 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 fine tuning of intracellular pH, cell volume control and systemic electrolyte, acid-base and fluid volume homeostasis. Here, we review the role of the Na+/H+ exchange mechanism as it relates to the physiology of organs and cells involved in nutrient 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 post-transcriptional levels. A particular emphasis is placed on Na+/H+ exchanger isoforms expressed on the apical (brush border) membrane of the epithelial cells, and the 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 Na+/H+ exchangers within the confines of the digestive system.