Chloride-dependent intracellular pH regulation via extracellular calcium-sensing receptor in the medullary thick ascending limb of the mouse kidney

Ulviyya Fizuli Aslanova, Tetsuji Morimoto, Elnur Ilham Farajov, Naonori Kumagai, Minako Nishino, Noriko Sugawara, Atsushi Ohsaga, Yoshio Maruyama, Shigeru Tsuchiya, Shori Takahashi, Yoshiaki Kondo

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The extracellular calcium-sensing receptor (CaSR) located in either luminal or basolateral cell membranes of various types of renal tubules including proximal tubules, Henle's loop and collecting ducts has been thought to play a fundamental role in electrolyte metabolism. To further identify the physiological roles of the CaSR, we examined the effects of Ca2+ and calcimimetics neomycin (Neo), gentamicin and gadolinium chloride (Gd3+) on the intracellular pH (pHi) of in vitro microperfused mouse medullary thick ascending limb (mTAL) cells of Henle's loop, by loading the cells with fluorescent pH indicator 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein and measuring the ratio of fluorescence emission at 530 nm after exciting the dye at 490 and 440 nm. In a steady-state condition in Hepes-buffered solution, the pHi in the mTALs was 7.29 ± 0.04 (n = 9). A concentration of 200 μmol/l Neo in the basolateral side decreased the pHi after 1 min by -0.13 ± 0.02 (n = 34, p < 0.0001). The other calcimimetics showed similar effects on pHi, whereas none of these calcimimetics in the lumen affected pHi. Na+ removal or the inhibition of Na+ and proton transport with amiloride, bumetanide, or bafilomycin did not eliminate the effect of Neo on pHi. On the other hand, Cl-removal clearly eliminated the Neo-induced pHi decrease (-0.06 ± 0.01 vs -0.00 ± 0.05 in Cl-removal, n = 4, p < 0.003). Thus, we have demonstrated for the first time that the CaSR is involved in the regulation of the pHi in the mTAL and requires Cl- to exert its effect.

Original languageEnglish
Pages (from-to)291-300
Number of pages10
JournalTohoku Journal of Experimental Medicine
Volume210
Issue number4
DOIs
Publication statusPublished - 05-12-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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