Calcium and calcimimetics regulate paracellular Na+ transport in the thin ascending limb of Henle's loop in mouse kidney.
The effect of Ca(2+) and calcimimetics on NaCl transport was investigated in the in vitro isolated microperfused mouse thin ascending limb of Henle's loop. In the presence of a transmural NaCl gradient, the transepithelial diffusional potential was 13.7 +/- 0.4 mV (n = 17). When the Ca(2+) in the bath was increased from 1.5 to 4.5 mM at 37 degrees C, the relative permeability of Na(+) to Cl(-) (P (Na) /P (Cl)) estimated from the diffusional voltage deflection due to the transepithelial NaCl gradient (V (d)) changed from 0.371 +/- 0.017 to 0.341 +/- 0.015 (n = 10, P < 0.0001). When the Ca(2+) in the lumen was increased from 1.5 to 4.5 mM, the P (Na) /P (Cl) decreased from 0.349 +/- 0.013 to 0.330 +/- 0.013 (n = 5, P < 0.002). The addition of 0.1 mM neomycin and 0.2 mM gentamicin to the bath or lumen also decreased the P (Na) /P (Cl). The same effect on P (Na) /P (Cl) of Ca(2+) and calcimimetics occurred in ClC-K1 (kidney-specific chloride channel) knockout mice. The addition of 300 mug/ml protamine to the bath strongly inhibited changes to P (Na) /P (Cl) induced by basolateral Ca(2+). These data indicate that ambient Ca(2+) and calcimimetics inhibit Na(+) transport in the thin ascending limb, which is known to occur via the paracellular shunt pathway. Our observations strongly suggest that Ca(2+) is involved in the regulation of paracellular Na(+) permeability in the thin ascending limbs.
Sugawara
Noriko
N
Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Morimoto
Tetsuji
T
Farajov
Elnur I
EI
Kumagai
Naonori
N
Aslanova
Ulviyya F
UF
Rai
Tatemitsu
T
Uchida
Shinichi
S
Sasaki
Sei
S
Tsuchiya
Shigeru
S
Kondo
Yoshiaki
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000172:deficiency / Q000235:genetics; D002712:Chlorides / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000494:pharmacology*; D066298:In Vitro Techniques; D017136:Ion Transport; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology*; D010477:Perfusion; D010539:Permeability; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011479:Protamines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D002118:Calcium; D018118:Chloride Channels; D002712:Chlorides; D002867:Chromones; D005839:Gentamicins; D009025:Morpholines; D009355:Neomycin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011479:Protamines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D012964:Sodium; C489933:Clcnka protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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