Essential hypertension is a disease resulting from the combined effects of genetic and environmental factors. The kidney plays a major role in the initiating and maintenance of hypertension. One of the determinants leading to Na⁺-sensitive hypertension in rats and humans is the cytoskeletal protein adducin. Milan Hypertensive Rats (MHS), an animal model for the pathology, are characterized by a raise of Na⁺,K⁺-ATPase activity and expression, due to a mutation of adducin. Patch-clamp experiments on MHS and MNS (Milan Normotensive Rats) DCT cells revealed the activity of a Cl^- channel with the same characteristics of CFTR, whose density and activity were significantly increased in MHS rats. By means of patch-clamp experiments, performed on NU12 (HEK cells stably transfected with the human WT adducin) and HU33 (HEK cells stably transfected with the G460W mutation) cells, a significantly higher and faster CFTR Cl- current was observed in presence of mutated adducin. Western blot and immunofluorescence experiments revealed that, in presence of mutated adducin, CFTR was more expressed in the plasmamembrane. FRET and coimmunoprecipitation experiments suggest that the interaction between CFTR and adducin, if existing, is weak in HEK cells. Yet, FRAP (Fluorescence Recovery After Photobleaching) experiments suggest that the mobility of CFTR is differently affected by WT or G460W adducin.

As a conclusion our data support the hypothesis that adducin influences CFTR mobility and activity.