Analysis of NaCl transport in thin ascending limb of Henle's loop in CLC-K1 null mice.
To characterize the nature of NaCl transport in the thin ascending limb (tAL), we examined the transport properties of Na(+) and Cl(-) using in vitro microperfusion of the tAL in CLC-K1 null mice. In the presence of a transmural NaCl concentration gradient (100 mM higher in the lumen), the transepithelial diffusion voltage (V(d)) was 15.5 +/- 1.0 and -7.6 +/- 1.4 mV in CLC-K1(+/+) and CLC-K1(-/-) mice, respectively. Neither Cl(-) transport inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) nor acidification of the bathing fluid changed the V(d) values in CLC-K1(-/-) mice. The addition of 300 microg/ml protamine, a selective blocker of paracellular conductance, to the bath increased the V(d) values by 5.6 +/- 0.7 and 12.6 +/- 1.5 mV (P < 0.001) in CLC-K1(+/+) and CLC-K1(-/-) mice, respectively. Although efflux coefficients of (36)Cl were significantly decreased in CLC-K1(-/-) mice (188.3 +/- 25.6 in 4 tubules vs. 17.2 +/- 7.0 x 10(-5) cm/s in 6 tubules), those of (22)Na were not different between CLC-K1(+/+) and CLC-K1(-/-) mice. These results clearly indicate that the major component of Cl(-) transport sensitive to NPPB or pH is mediated by CLC-K1 in the tAL.
Liu
Wen
W
Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Morimoto
Tetsuji
T
Kondo
Yoshiaki
Y
Iinuma
Kazuie
K
Uchida
Shinichi
S
Sasaki
Sei
S
Marumo
Fumiaki
F
Imai
Masashi
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004553:Electric Conductivity; D006493:Heparin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007671:Kidney Concentrating Ability / Q000502:physiology*; D007679:Kidney Medulla / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009579:Nitrobenzoates / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011868:Radioisotopes; D026941:Sodium Channel Blockers / Q000494:pharmacology; D012965:Sodium Chloride / Q000378:metabolism*; D012979:Sodium Radioisotopes
D020533:Angiogenesis Inhibitors; D000925:Anticoagulants; D018118:Chloride Channels; C489933:Clcnka protein, mouse; D009579:Nitrobenzoates; D011479:Protamines; D011868:Radioisotopes; D026941:Sodium Channel Blockers; D012979:Sodium Radioisotopes; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D012965:Sodium Chloride; D006493:Heparin