TY - JOUR
T1 - Cystic fibrosis transmembrane conductance regulator differentially regulates human and mouse epithelial sodium channels in Xenopus oocytes
AU - Yan, Wusheng
AU - Samaha, Frederick F.
AU - Ramkumar, Mohan
AU - Kleyman, Thomas R.
AU - Rubenstein, Ronald C.
PY - 2004/5/28
Y1 - 2004/5/28
N2 - The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl- channel properties, regulates other ion channels. CFTR inhibits murine or rat epithelial Na+ channel (mENaC of rENaC) currents in many epithelial and non-epithelial cells, whereas murine or rat ENaC increases CFTR functional expression. These regulatory interactions are reproduced in Xenopus oocytes where both the open probability and surface expression of wild type CFTR Cl- channels are increased when CFTR is co-expressed with αβγ mENaC, and conversely the activity of mENaC is inhibited after wild type CFTR activation. Using the Xenopus oocyte expression system, differences in functional regulatory interactions were observed when CFTR was co-expressed with either αβγ mENaC or αβγ human ENaC (hENaC). Co-expression of CFTR and αβγ mENaC or hENaC resulted in an ∼3-fold increase in CFTR Cl- current compared with oocytes expressing CFTR alone. Oocytes co-injected with both CFTR and mENaC of hENaC expressed an amiloride-sensitive whole cell current that was decreased compared with that observed with the injection of mENaC or hENaC alone before CFTR activation with forskolin/3-isobutyl-1-methylxanthine. CFTR activation resulted in a further 50% decrease in mENaC-mediated currents, an ∼20% decrease in α-T663-hENaC-mediated currents, and essentially no change in α-A663-hENaC-mediated currents. Changes in ENaC functional expression correlated with ENaC surface expression by oocyte surface biotinylation experiments. Assessment of regulatory interactions between CFTR and chimeric mouse/human ENaCs suggest that the 20 C-terminal amino acid residues of α ENaC confer species specificity regarding ENaC inhibition by activated CFTR.
AB - The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl- channel properties, regulates other ion channels. CFTR inhibits murine or rat epithelial Na+ channel (mENaC of rENaC) currents in many epithelial and non-epithelial cells, whereas murine or rat ENaC increases CFTR functional expression. These regulatory interactions are reproduced in Xenopus oocytes where both the open probability and surface expression of wild type CFTR Cl- channels are increased when CFTR is co-expressed with αβγ mENaC, and conversely the activity of mENaC is inhibited after wild type CFTR activation. Using the Xenopus oocyte expression system, differences in functional regulatory interactions were observed when CFTR was co-expressed with either αβγ mENaC or αβγ human ENaC (hENaC). Co-expression of CFTR and αβγ mENaC or hENaC resulted in an ∼3-fold increase in CFTR Cl- current compared with oocytes expressing CFTR alone. Oocytes co-injected with both CFTR and mENaC of hENaC expressed an amiloride-sensitive whole cell current that was decreased compared with that observed with the injection of mENaC or hENaC alone before CFTR activation with forskolin/3-isobutyl-1-methylxanthine. CFTR activation resulted in a further 50% decrease in mENaC-mediated currents, an ∼20% decrease in α-T663-hENaC-mediated currents, and essentially no change in α-A663-hENaC-mediated currents. Changes in ENaC functional expression correlated with ENaC surface expression by oocyte surface biotinylation experiments. Assessment of regulatory interactions between CFTR and chimeric mouse/human ENaCs suggest that the 20 C-terminal amino acid residues of α ENaC confer species specificity regarding ENaC inhibition by activated CFTR.
UR - http://www.scopus.com/inward/record.url?scp=2542500548&partnerID=8YFLogxK
U2 - 10.1074/jbc.M402373200
DO - 10.1074/jbc.M402373200
M3 - Article
C2 - 15047694
AN - SCOPUS:2542500548
SN - 0021-9258
VL - 279
SP - 23183
EP - 23192
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -