Cystic fibrosis gene encodes a cAMP-dependent chloride channel in heart.
cAMP-dependent chloride channels in heart contribute to autonomic regulation of action potential duration and membrane potential and have been inferred to be due to cardiac expression of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In this report, a cDNA from rabbit ventricle was isolated and sequenced, which encodes an exon 5 splice variant (exon 5-) of CFTR, with >90% identity to human CFTR cDNA present in epithelial cells. Expression of this cDNA in Xenopus oocytes gave rise to robust cAMP-activated chloride currents that were absent in control water-injected oocytes. Antisense oligodeoxynucleotides directed against CFTR significantly reduced the density of cAMP-dependent chloride currents in acutely cultured myocytes, thereby establishing a direct functional link between cardiac expression of CFTR protein and an endogenous chloride channel in native cardiac myocytes.
Hart
P
P
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89557-0046, USA.
Warth
J D
JD
Levesque
P C
PC
Collier
M L
ML
Geary
Y
Y
Horowitz
B
B
Hume
J R
JR
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics* / Q000502:physiology; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary; D005091:Exons; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D016276:Ventricular Function; D014981:Xenopus
C505032:CFTR protein, human; D018118:Chloride Channels; D018076:DNA, Complementary; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP