Evidence for apical sodium proton exchange in macula densa cells

Academic Article


  • These studies were performed to determine if changes in luminal sodium chloride concentration ([NaCl]) might alter macula densa intracellular pH. Isolated thick ascending limbs with attached glomeruli were bathed in a 150 mM NaCl Ringer's solution and perfused in vitro with a 25 mM NaCl solution; N-methyl-D-glucamine cyclamate was used to substitute for NaCl. Macula densa cells were loaded with BCECF and intracellular pH was monitored using a microscope based-dual excitation photometer system. Control intracellular pH for all experiments in which tubules were initially perfused with 25 mM NaCl averaged 7.22 ± 0.06; N = 28. Increasing luminal [NaCl] from 25 to 150 mM elevated macula densa pH by 0.15 ± 0.03 (N = 6; P < 0.05) while increasing just luminal [Na] from 25 to 150 mM alkalinized macula densa cells by 0.17 ± 0.05 (N = 6; P < 0.05). In addition, there was a highly significant linear relationship between luminal [Na] and intracellular pH between 25 and 150 mM NaCl. Other studies were performed to assess the effects of amiloride, an inhibitor of Na:H exchange, on macula densa intracellular pH. Addition of amiloride, to the 25 mM NaCl perfusate acidified macula densa cells by 0.09 ± 0.03 (N = 6; P < 0.001) and significantly attenuated the increase in pH obtained when luminal [NaCl] was raised from 25 to 150 mM. Other studies evaluated the effects of inhibition of Na:2Cl:K cotransport on macula densa pH. Furosemide (50 μM) alkalinized macula densa pH by 0.11 ± 0.02 (N = 5; P < 0.01) in the presence of 25 mM NaCl in the lumen whereas amiloride entirely reversed the furosemide-induced alkalinization in these cells. These results demonstrate that changes in either luminal [NaCl] or furosemide-sensitive NaCl transport can alter macula densa intracellular pH presumably by varying the Na gradient across the apical membrane. The results of these studies are consistent with the existence of an apical Na:H antiporter in macula densa cells.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 22909825
  • Author List

  • Fowler BC; Chang YS; Laamarti A; Higdon M; Lapointe JY; Bell PD
  • Start Page

  • 746
  • End Page

  • 751
  • Volume

  • 47
  • Issue

  • 3