An Outwardly Rectifying Chloride Channel in Human Atrial Cardiomyocytes

INTRODUCTION: 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, PCl/PNa= 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.