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.

Gestational length affects a change in the transepithelial voltage and the rNKCC2 expression pattern in the ascending thin limb of Henle's loop.

To examine whether the functional and morphologic conversion of the neonatal ascending thin limb (ATL) of Henle's loop is related to gestational length, we evaluated the transepithelial voltages (Vts) of ATLs in perinatal mouse, hamster, rabbit, and rat kidneys. In isolated microperfused tubule preparations, Vts of neonatal ATLs were 23.8 +/- 1.4 in mouse, 25.7 +/- 2.2 in hamster, and 18.2 +/- 1.6 mV in rabbit. The influence of gestational length on the Vts and rat Na-K-Cl cotransporter (rNKCC2) expression pattern was also examined in perinatal rats subjected to a prolonged gestation due to either a daily s.c. injection of 5 mg progesterone or ligation of the extremities of the uterine horn. Vts of d 3 neonates were 2.9 +/- 1.0 (p < 0.0001 versus d 0); Vts of d 23 fetuses subjected to ligation were 4.9 +/- 0.8 (p < 0.005 versus d 0); and Vts of d 23 fetuses given progesterone were 3.4 +/- 1.7 mV (p < 0.001 versus d 0). rNKCC2 expression tended to disappear in the renal papillae of d 23 fetuses. Our data demonstrate that the perinatal conversion of the ATL is a phenomenon commonly observed among rodents; furthermore, it is dependent on the gestational length, but unrelated to the birth process.