Absorption across the Thick Ascending Limb Is Not Altered in Cystic Fibrosis Mice

The cortical thick ascending limb (CTAL) absorbs Cl 2 via a Na 1 -K 1 -Cl 2 cotransport at the apical membrane and several Cl 2 channels at the basolateral membrane, including a 9-pS channel having several properties of the cystic fibrosis transmembrane conductance regulator (CFTR). Having checked that CFTR mRNA is present in the mouse CTAL, we investigated whether this channel is a CFTR molecule by applying the patch-clamp technique to CTALs microdissected from CFTR knockout mice ( cftr m1Unc ). The 9-pS channel was active in cell-attached patches from tubules of mice homozygous for the disrupted cftr gene [CFTR ( 2 / 2 )] at the same frequency and with the same activity ( NP o ) as in normal [CFTR ( 1 / 1 )] or heterozygous [CFTR ( 1 / 2 )] mice. The conductive properties of the channel, studied on inside-out patches, were identical in CFTR ( 2 / 2 ), CFTR ( 1 / 1 ), and CFTR ( 1 / 2 ) tubules, as were the sensitivities to internal pH and internal ATP, two typical features of this channel. In addition, the Cl 2 absorption in isolated, microperfused CTALs and the Na 1 -K 1 -Cl 2 cotransport activity were identical in CFTR ( 2 / 2 ), CFTR ( 1 / 1 ), and CFTR ( 1 / 2 ) mice. These results show that the 9-pS Cl 2 channel is distinct from CFTR, and that the CFTR protein has no influence on the Cl 2 absorption in this part of the renal tubule. ( J. Clin. Invest. 1998. 102:1986–1993.)