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Characterization of basolateral chloride/bicarbonate exchange in macula densa cells

¹Departments of Medicine and Physiology, Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama; ²The Water and Salt Research Center and Institute of Anatomy, University of Aarhus, Aarhus C, Denmark; ³Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary; and ⁴Department of Physiology and Biophysics and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California

Submitted 3 August 2004 ; accepted in final form 10 October 2004

Functional and immunohistological studies were performed to identify basolateral chloride/bicarbonate exchange in macula densa cells. Using the isolated, perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pH_i) was measured with fluorescence microscopy and BCECF. For these experiments, basolateral chloride was reduced, resulting in reversible macula densa cell alkalinization. Anion exchange activity was assessed by measuring the maximal net base efflux on readdition of bath chloride. Anion exchange activity required the presence of bicarbonate, was independent of changes in membrane potential, did not require the presence of sodium, and was inhibited by high concentrations of DIDS. Inhibition of macula densa anion exchange activity by basolateral DIDS increased luminal NaCl concentration-induced elevations in pH_i. Immunohistochemical studies using antibodies against AE2 demonstrated expression of AE2 along the basolateral membrane of macula densa cells of rabbit kidney. These results suggest that macula densa cells functionally and immunologically express a chloride/bicarbonate exchanger at the basolateral membrane. This transporter likely participates in the regulation of pH_i and might be involved in macula densa signaling.

chloride/bicarbonate antiporters; acid-base equilibrium; juxtaglomerular apparatus; sodium/hydrogen antiporters

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