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 beta and gamma, but not alpha ENaC. Temporal regulation of beta and gamma ENaC by PKC differed; gamma ENaC decreased with a time constant of 3.7 +/- 1.0 h, whereas beta ENaC decreased in 13.9 +/- 3.0 h. Activation of PRC also resulted in a decrease in trans-epithelial Na+ reabsorption for up to 48 h. PIMA activation of PRC resulted in negative feedback inhibition of PKC protein levels beginning within 4 h, Both beta and gamma ENaC 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 PRC differentially regulates ENaC subunit levels by decreasing the levels of beta and gamma but not alpha ENaC protein. These results imply a PKC-dependent, long term decrease in Na+ reabsorption.