Na+/H+ Exchange in Human Lymphocytes and Platelets in Chronic and Subacute Metabolic Acidosis

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The effect of acid-base disturbances on sodium/proton (Na+/H+) exchange has been examined in animal models; however, few data are available from human studies. To test the effect of metabolic acidosis on Na (+)/H+ exchange in man, as well as to examine the relationship between Na+/H+ exchange and cytosolic calcium ((Ca2+)i), we measured both variables in patients with decreased renal function with mild metabolic acidosis (pH 7.34+/-0.06), in normal control subjects (pH 7.41+/-0.02), and in subjects before (pH 7.40+/-0.01), and after (pH 7.26+/-0.04) ammonium chloride (NH4 Cl) 15 g for 5 d. Lymphocytes and platelets were loaded with the cytosolic pH (pHi) indicator 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein and acidified to pH (approximately)6.6 with propionic acid. To quantitate Na+/H+ exchange, dpHi/dt was determined at 1 min. (Ca2+)i was measured with fura-2. Na+/H+ exchange was significantly increased only in lymphocytes of patients with renal insufficiency. Neither intracellular pH (pHi) nor (Ca2+)i was different from controls. NH4 Cl resulted in a significant increase in Na+/H+ exchange in lymphocytes, but not in platelets of normal subjects. Values of pHi and (Ca2+)i in either cell type remained unaffected. Since metabolic acidosis influenced Na+/H+ only in lymphocytes, but not in platelets, it is possible that protein synthesis may be involved in increasing Na+/H+ exchange. (J. Clin. Invest. 1993. 92:858-865.) Key words: Na+/H+ antiporter. lymphocytes. platelets. acidosis. renal failure

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