Cl- channels in CF: lack of activation by protein kinase C and cAMP-dependent protein kinase.
Secretory chloride channels can be activated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in normal airway epithelial cells but not in cells from individuals with cystic fibrosis (CF). In excised, inside-out patches of apical membrane of normal human airway cells and airway cells from three patients with CF, the chloride channels exhibited a characteristic outwardly rectifying current-voltage relation and depolarization-induced activation. Channels from normal tissues were activated by both cAMP-dependent protein kinase and protein kinase C. However, chloride channels from CF patients could not be activated by either kinase. Thus, gating of normal epithelial chloride channels is regulated by both cAMP-dependent protein kinase and protein kinase C, and regulation by both kinases is defective in CF.
Hwang
T C
TC
Department of Physiology, Johns Hopkins University, Baltimore, MD 21205.
Lu
L
L
Zeitlin
P L
PL
Gruenert
D C
DC
Huganir
R
R
Guggino
W B
WB
D000328:Adult; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004594:Electrophysiology; D005333:Fetus; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology / Q000503:physiopathology
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D011494:Protein Kinases; D011493:Protein Kinase C