The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes.

Abstract

SUMMARY. The plasma membranes of most if not all vertebrate cells contain a transport system that mediates the transmembrane exchange of sodium for hydrogen. The kinetic properties of this transport system include a 1:1 stoichiometry, affinity for lithium and ammonium ion in addition to sodium and hydrogen, the ability to function in multiple 1:1 exchange modes involving these four cations, sensitivity to inhibition by amiloride and its analogues, and allosteric regulation by intracellular protons. The plasma membrane sodium-hydrogen exchanger plays a physiological role in the regulation of intracellular pH, the control of cell growth and proliferation, stimulusresponse coupling in white cells and platelets, the metabolic response to hormones such as insulin and glucocorticoids, the regulation of cell volume, and the transepithelial absorption and secretion of sodium, hydrogen, bicarbonate and chloride ions, and organic anions. Preliminary evidence raises the possibility that the sodium-hydrogen exchanger may play a pathophysiological role in such diverse conditions as renal acid-base disorders, essential hypertension, cancer, and tissue or organ hypertrophy. Thus, future research on cellular acid-base homeostasis in general, and on plasma membrane sodium-hydrogen exchange in particular, will enhance our understanding of a great variety of physiological and pathophysiological processes. (Circ Res 57: 773-788, 1985)

Leucocyte Na+/H+ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy

“…Thus, diabetic nephropathy may develop in diabetic patients who are also susceptible to essential hypertension [6,9]. It has been suggested that this exchange may be a mode of operation of the Na+/H + antiport [11]. However, the anucleate erythrocyte does not exhibit Na+/H + exchange at rest [22] and thus is not suitable for measurements of Na § + ant• activity.…”

“…Mahnensmith and Aronson have suggested that this countertransport may be one mode of operation of the ubiquitous Na +/H § antiport [11]. Increased Na +/H + antiport activity was subsequently documented in platelets [12] and leucocytes from hypertensive humans [13,14] and in the spontaneously hypertensive rat [15,16].…”

Regulation of Intracellular pH in Single Rat Cortical Neurons in vitro: A Microspectrofluorometric Study

“…This ex changer would adjust pHj during alkaline transients or could serve to accumulate Cl-in cells. In most vertebrate cells studied, pHj regulation during acid transients is achieved by an amiloride-sensitive N a + IH + anti porter , often working in conjunction with Na + -dependent or Na + -independent HC03 -1 Cl-exchangers (Mahnensmith and Aronsson, 1985;Boyarsky et aI., 1988b;Frelin et aI., 1988;Grinstein et aI., 1989). Recent studies have identified addi tional mechanisms that influence pHi' e.g., an elec trogenic N a + IHC03 -symporter, which carries HC03 -inward at the expense of the Na + gradient (Boron and Boulpaep, 1983;Deitmer and Schlue, 1987; for reviews see Madshus, 1988;Chesler and Kaila, 1992).…”

Urinary retinol-binding protein (RBP) excretion and erythrocyte sodium-lithium countertransport (SLC) activity in a cohort of healthy normotensive subjects

“…SLC activity could be indicative of plasma membrane SHE; the expression of which is repeated in cell types other than erythrocytes. 12 This hypothesis is appealing since it is easy to envisage how a dysfunction of the SHE in vascular smooth muscle (VSM) or kidney cells could contribute to development of hypertension. Increased SHE could result in an increased sodium influx.…”