CFTR chloride channels in human and simian heart

Area of Science:

• Cardiology
• Molecular Biology
• Ion Channel Physiology

Background:

• The cAMP-dependent chloride (Cl-) conductance in the heart is attributed to cardiac expression of the cystic fibrosis transmembrane conductance regulator (CFTR).
• While CFTR cardiac isoforms are known in some species, their expression in primate hearts remains largely uncharacterized.

Purpose of the Study:

• To investigate the molecular and functional expression of CFTR in human and simian cardiac tissues.
• To determine the presence and activity of cAMP-dependent Cl- currents in isolated human atrial and simian ventricular cells.

Main Methods:

• Reverse transcription polymerase chain reaction (RT-PCR) was used to detect CFTR transcripts in human and simian atrial and ventricular mRNA.
• Whole-cell and giant inside-out patch-clamp techniques were employed to assess functional expression of Cl- currents in isolated cardiac myocytes.

Main Results:

• RT-PCR and Southern blot analysis confirmed the expression of both spliced and unspliced CFTR transcripts in human and simian atrial and ventricular tissues.
• Functional studies revealed a forskolin (FSK)-activated, DIDS-insensitive Cl- conductance in human atrial and simian ventricular myocytes.
• Patch-clamp recordings identified unitary Cl- channels in human atrial myocytes resembling CFTR channels, activated by protein kinase A (PKA).

Conclusions:

• This study provides clear molecular evidence for CFTR expression in human and simian myocardium.
• Electrophysiological data support the functional expression of CFTR Cl- channels in primate cardiac tissue.