Ca2+-activated Cl- current reduces transmural electrical heterogeneity within the rabbit left ventricle

Objective: Various cationic membrane channels contribute to the heterogeneity of action potential configuration between the transmural layers of the left ventricle. The role of anionic membrane channels is less intensively studied. We investigated the role of the Ca2+-activated Cl- current, I-Cl(Ca), in transmural electrical heterogeneity. Methods and Results: We determined the density of I-Cl(Ca) and its physiological role in subepicardial and subendocardial ventricular myocytes of rabbit using the patch-clamp technique. I-Cl(Ca) was measured as the 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitive current. The current-voltage relationships and the densities of I-Cl(Ca) were similar in subepicardial and subendocardial myocytes. However, the functional role of I-Cl(Ca) exhibited striking differences. In subendocardial myocytes, blockade of I-Cl(Ca) by DIDS increased action potential duration (APD) significantly at all measured stimulus frequencies (3.33-0.2 Hz). In subepicardial myocytes, I-Cl(Ca) blockade increased APD only at 3.33 Hz, but not at the lower stimulus frequencies. At 1 Hz, I-Cl(Ca) blockade in subepicardial myocytes only caused an APD increase when the transient outward K+ current, I-to1, was blocked. Conclusions: The densities and gating properties of I-Cl(Ca) are similar in subepicardial and subendocardial myocytes. I-Cl(Ca) contributes to APD shortening in subendocardial, but not in subepicardial myocytes except at 3.33 Hz. These differences in functional expression of I-Cl(Ca) reduce the electrical heterogeneity in rabbit left ventricle