ALTERNATIVE SPLICING OF CFTR CL- CHANNELS IN HEART

We have previously demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels are expressed in heart (Levesque et al., Circ. Res. 71: 1002-1007, 1992). However, the structural identity between this cardiac protein and CFTR in epithelial cells is unknown. We amplified cDNA from rabbit ventricle and cloned fragments corresponding to the 12 transmembrane spanning domains of the epithelial CFTR transcript. The deduced sequence from rabbit heart indicated deletion of a 30-amino acid segment in the first cytoplasmic loop of CFTR, which corresponds to known locations of intron-exon junctions bordering exon 5 in the CFTR gene, suggesting that CFTR is alternatively spliced in heart. Outside this region, the heart CFTR isoform displayed >95% identity to human epithelial CFTR. Molecular analysis demonstrated CFTR expression only in cardiac tissues that exhibited a adenosine 3',5'-cyclic monophosphate-dependent Cl- conductance in native cells. The expression of a specific isoform of CFTR Cl- channels in mammalian heart may have functional and clinical significance.