The Role of Transmembrane Chloride Current in Afterdepolarisations in Canine Ventricular Cardiomyocytes

Abstract. The physiological role of chloride currents (ICl) in cardiac cells is poorly understood. The aim of the present study was to reveal the role of ICl in the genesis of early and delayed afterdepolarisations (EADs and DADs, respectively). First we identi ed ICl under action potential voltage clamp conditions as the anthracene-9-carboxylic acid (ANTRA) (0.5 mmol/l)-sensitive current. The ANTRA-sensitive current was large and outwardly directed at the beginning, while it was moderate and inwardly directed at the end of the action potential. Application of ANTRA under current clamp conditions decreased the depth of the incisura, shifted the plateau upwards and lengthened the duration of action potentials. The eect of ANTRA was studied in three models of afterdepolarisations: the ouabain-induced DAD model, the caesium-induced EAD model, and in the presence of subthreshold concentration of isoproterenol. Preincubation of the cells with 0.5 mmol/l ANTRA failed to induce afterdepolarisations. Ouabain (200 nmol/l) alone caused DADs in 62.5 % of the cells within 15 min. When ouabain was applied in the presence of ANTRA, 60 % of the myocytes transiently displayed EADs before th