Ritter M, Fuerst J, Wöll E, Chwatal S, Gschwentner M, Lang F, Deetjen P, Paulmichl M
Department of Physiology, University of Innsbruck, Austria.
Cell Physiol Biochem. 2001;11(1):1-18. doi: 10.1159/000047787.
The Na(+)/H(+) exchangers (NHEs) are among the major ion transporters involved in cell volume regulation. NHE activation leads to a cellular influx of Na(+) ions and extrusion of H(+) ions, which are readily replenished from intracellular buffers. This will result in a net import of Na(+). In many systems NHE operates in parallel to Cl(-)/ HCO3(-) exchange, resulting in cellular uptake of NaCl. The influx of osmotically obliged water will consequently lead to cell swelling. This makes NHEs suitable to serve as powerful mechanisms for increasing cell volume (CV). The low volume threshold for NHE activation enables the cells to respond to very minute reductions of the CV. By the coupling to the export of H(+) ions cell volume regulatory NHE activation may lead to changes in intracellular pH. On the other hand NHEs are activated by a broad variety of ligands and by intracellular acidosis, which, in turn, may consequently lead to cell swelling. In addition, NHEs are linked to other intracellular proteins and structures, like e.g. the cytoskeleton, which themelves are involved in the regulation of numerous cellular processes. Therefore NHEs link CV regulation to a diversity of cellular functions, both in physiological and pathophysiological conditions. Six isoforms of the Na(+)/H(+) exchanger, termed NHE1--6, have been cloned so far. NHE 1--5 are located in the plasma membrane, whereas NHE6 is sorted to the mitochondrial membrane. NHE1 and NHE6 are the ubiquitously expressed isoforms. The expression of the isoforms NHE2 to NHE5 is restricted to specific tissues and the pattern of their expression, as well as their subcellular localization indicate that they fulfill specialized functions. Cell shrinkage induced activation has been shown for NHE1,2 and 4. In contrast, NHE3 is inhibited by cell shrinkage. In many cells several isoforms are present and assigned to specific membrane domains where they may serve a functional crosstalk between the different ion transporters.
钠氢交换体（NHEs）是参与细胞体积调节的主要离子转运体之一。NHE激活导致钠离子细胞内流和氢离子排出，这些氢离子可从细胞内缓冲液中轻易补充。这将导致钠离子的净内流。在许多系统中，NHE与氯/碳酸氢根交换平行运作，导致细胞摄取氯化钠。因此，渗透性必需水的内流将导致细胞肿胀。这使得NHEs成为增加细胞体积（CV）的有力机制。NHE激活的低体积阈值使细胞能够对CV的非常微小的降低做出反应。通过与氢离子排出相偶联，细胞体积调节性NHE激活可能导致细胞内pH值的变化。另一方面，NHEs被多种配体和细胞内酸中毒激活，这反过来又可能导致细胞肿胀。此外，NHEs与其他细胞内蛋白质和结构相连，例如细胞骨架，而细胞骨架本身参与众多细胞过程的调节。因此，在生理和病理生理条件下，NHEs将CV调节与多种细胞功能联系起来。到目前为止，已经克隆出钠氢交换体的六种亚型，称为NHE1 - 6。NHE 1 - 5位于质膜，而NHE6分选至线粒体膜。NHE1和NHE6是普遍表达的亚型。NHE2至NHE5亚型的表达局限于特定组织，它们的表达模式以及亚细胞定位表明它们发挥着特定的功能。已显示NHE1、2和4可被细胞收缩诱导激活。相反，NHE3被细胞收缩抑制。在许多细胞中存在几种亚型，并分配到特定的膜结构域，在那里它们可能在不同离子转运体之间发挥功能性串扰作用。
