MOLECULAR PHYSIOLOGY OF CARDIAC CHLORIDE CHANNELS

The polymerase chain reaction (PCR) was used to amplify four distinct regions corresponding to the cardiac cystic fibrosis transmembrane con ductance regulator (CFTR) gene product from several cardiac tissues to determine if the molecular distribution of CFTR matches the distribut ion of cAMP-dependent Cl- channels in native myocytes. Amplification o f the regions corresponding to NBD1, transmembrane segments (TSs) VII- XII, and the R domain showed a precise correlation to tissues that ele ctrophysiologically exhibit cAMP-dependent Cl- channels, whereas regio n TS I-VI exhibited a distribution independent of the presence of cAMP -dependent Cl- channels. In giant excised membrane patches from human atrial myocytes, 10pS single Cl- channels activated by protein kinase A could be detected, suggesting that functional CFTR Cl- channels are expressed in human atrial myocardium.