Differential effects of protein kinase C on the levels of epithelial Na⁺ channel subunit proteins

Regulation of epithelial Na⁺ channel (ENaC) subunit levels by protein kinase C (PKC) was investigated in A6 cells. PKC activation altered ENaC subunit levels, differentially decreasing the levels of both β and γ, but not αENaC. Temporal regulation of β and γENaC by PKC differed; γENaC decreased with a time constant of3.7 ± 1.0 h, whereas βENaC decreased in 13.9 ±3.0h. Activation of PKC also resulted in a decrease in trans-epithelial Na⁺ reabsorption for up to 48h. PMA activation of PKC resulted in negative feedback inhibition of PKC protein levels beginning within 4h. Both β and γENaC levels, as well as transport tended toward pretreatment values after 48 h of PMA treatment. PKC inhibitors attenuated the effects of PMA on ENaC subunit levels and Na⁺ transport. These results directly show for the first time that PKC differentially regulates ENaC subunit levels by decreasing the levels of β and γ but not αENaC protein. These results imply a PKC-dependent, long term decrease in Na⁺ reabsorption.