Premium
An Outwardly Rectifying Chloride Channel in Human Atrial Cardiomyocytes
Author(s) -
DEMION MARIE,
GUINAMARD ROMAIN,
EL CHEMALY ANTOUN,
RAHMATI MOHAMMAD,
BOIS PATRICK
Publication year - 2006
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2005.00255.x
Subject(s) - medicine , cardiology , atrial fibrillation , chloride channel , biophysics , biology
Among a range of chloride channels, outwardly rectifying Cl − channels have been reported in the heart of various species. Although the anionic current carried by this channel has been subjected to intense electrophysiological investigations, paradoxically no examination of single‐channel currents has been reported for human cardiomyocytes. Methods and Results: Using the cell‐attached and cell‐free configurations of the patch‐clamp technique, we have characterized the properties of an outwardly rectifying chloride current (ORCC) at the unitary level in freshly isolated human atrial cardiomyocytes. In excised inside‐out patches, the channel presented a nonlinear I/V relationship with a conductance of 76.5 ± 14.7 pS in the positive voltage range and 8.1 ± 2 pS in the negative voltage range, indicating an outward rectification. Preincubation with the protein kinase C activator phorbol 12‐myristate 13‐acetate (PMA) significantly increased the number of spontaneously active channels observed. The channel was Cl − selective (Cl − to Na + permeability ratio, P Cl /P Na = 18) with the permeability sequence I − > Br − > Cl − > F − > gluconate. It was blocked by the classical Cl − channels blockers glibenclamide, NPPB, SITS, and DIDS. Channel activity was not dependent upon internal calcium concentration. In the cell‐attached configuration, ORCC channel activation was observed under perfusion of a hypotonic solution. Conclusion: Human atrial myocytes express an outwardly rectifying Cl − channel that is sensitive to PKC activation. This channel shares biophysical and pharmacological properties with the swelling‐activated chloride current implicated in cardiac pathologies such as myocardial ischemia and dilated cardiopathies.