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Am J Physiol Cell Physiol 276: C711-C716, 1999;
0363-6143/99 $5.00
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Vol. 276, Issue 3, C711-C716, March 1999

Incubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH

Morimasa Amemiya1, Kaoru Tabei1, Eiji Kusano1, Yasushi Asano1, and Robert J. Alpern2

1 Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan 329-0498; and 2 University of Texas Southwestern Medical Center, Dallas, Texas 75235-8856

Chronic hypokalemia increases the activity of proximal tubule apical membrane Na+/H+ antiporter NHE3. The present study examined the effect of the incubation of OKP cells (an opossum kidney, clone P cell line) in control medium {K+ concn ([K+]) = 5.4 mM} or low-K+ medium ([K+] = 2.7 mM) on NHE3. The activity of an ethylisopropyl amiloride-resistant Na+/H+ antiporter, whose characteristics were consistent with those of NHE3, was increased in low-K+ cells beginning at 8 h. NHE3 mRNA and NHE3 protein abundance were increased 2.2-fold and 62%, respectively, at 24 h but not at 8 h. After incubation in low-K+ medium, intracellular pH (pHi) decreased by 0.27 pH units (maximum at 27 min) and then recovered to the control level. Intracellular acidosis induced by 5 mM sodium propionate increased Na+/H+ antiporter activity at 8 and 24 h. Herbimycin A, a tyrosine kinase inhibitor, blocked low-K+- and sodium propionate-induced activation of the Na+/H+ antiporter at 8 and 24 h. Our results demonstrate that low-K+ medium causes an early decrease in pHi, which leads to an increase in NHE3 activity via a tyrosine kinase pathway.

sodium/hydrogen antiporter; tyrosine kinase; low potassium; proximal tubule; opossum kidney, clone P cells


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