Expression of cystic fibrosis transmembrane regulator Cl- channels in heart.
Cyclic AMP (cAMP)-dependent chloride channels modulate changes in resting membrane potential and action potential duration in response to autonomic stimulation in heart. A growing body of evidence suggests that there are marked similarities in the properties of the cAMP-dependent chloride channels in heart and cystic fibrosis transmembrane regulator (CFTR) chloride channels found in airway epithelia or in cells expressing the CFTR gene product. We isolated poly A+ mRNA from rabbit ventricle and converted it to cDNA for amplification using the polymerase chain reaction (PCR). A fragment corresponding to the nucleotide-binding domain 1 (NBD1) of the CFTR transcript was cloned. Comparison of the amino acid sequence of NBD1 of human CFTR with the deduced sequence of the rabbit heart PCR product indicated 98% identity. Northern blot analysis, using the heart amplification product as a cDNA probe, demonstrated expression of homologous transcripts in human atrium, guinea pig and rabbit ventricle, and dog pancreas. Xenopus oocytes injected with poly A+ mRNA extracted from rabbit and guinea pig ventricle or dog pancreas expressed robust time-independent chloride currents in response to an elevation of cAMP. We conclude that CFTR chloride channels are expressed in heart and are responsible for the observed cAMP-dependent chloride conductance.
Levesque
P C
PC
Department of Physiology, University of Nevada School of Medicine, Reno 89557-0046.
Hart
P J
PJ
Hume
J R
JR
Kenyon
J L
JL
Horowitz
B
B
D000818:Animals; D015152:Blotting, Northern; D018118:Chloride Channels; D002712:Chlorides; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006801:Humans; D007473:Ion Channels; D008564:Membrane Potentials; D008565:Membrane Proteins; D009865:Oocytes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D014158:Transcription, Genetic; D014982:Xenopus laevis
C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP