Cl- absorption across the thick ascending limb is not altered in cystic fibrosis mice - A role for a pseudo-CFTR Cl- channel

The cortical thick ascending limb (CTAL) absorbs Cl- via a Na+-K+-Cl- cotra nsport at the apical membrane and several Cl- channels at the basolateral m embrane, including a 9-pS channel having several properties of the cystic f ibrosis transmembrane conductance regulator (CFTR), Having checked that CFT R mRNA is present in the mouse CTAL, we investigated whether this channel i s a CFTR molecule by applying the patch-clamp technique to CTALs microdisse cted from CFTR knockout mice (cftr(m1Unc)). The 9-pS channel was active in cell-attached patches from tubules of mice homozygous for the disrupted cft r gene [CFTR (-/-)] at the same frequency and with the same activity (NPo) as in normal [CFTR (+/+)] or heterozygous [CFTR (+/-)] mice. The conductive properties of the channel, studied an inside-out patches, were identical i n CFTR (-/-), CFTR (+/+), and CFTR (+/-) tubules, as were the sensitivities to internal pH and internal ATP, two typical features of this channel, In addition, the Cl- absorption in isolated, microperfused CTALs and the Na+-K +-Cl- cotransport activity were identical in CFTR (-/-), CFTR (+/+), and CF TR (+/-) mice. These results show that the 9-pS Cl- channel is distinct fro m CFTR, and that the CFTR protein has no influence on the Cl- absorption in this part of the renal tubule.