Antiarrhythmic peptides enhance gap junction current in pairs of cardiomyocytes and coupling in cardiac tissue. To elucidate the underlying mechanisms, we investigate the effects of the antiarrhythmic peptide AAP10 (NH2-Gly-Ala-Gly-4Hyp-Pro-Tyr-COOH) on pairs of adult guinea pig ventricular cardiomyocytes. By using a double-cell voltage clamp technique in pairs of cardiomyocytes, we found that gap junction conductance steadily decreased with time (by -343 ± 208 pS/min [Schaefer et al. 1999]). Under control conditions using 50nmol/L AAP10 reversed this rundown and increased gap junction conductance (by +406 ± 219 pS/min, P Conclusions: 1) AAP10 increases gap junction conductance in adult cardiomyocytes, 2) AAP10 exerts its effect via enhanced PKCα-dependent phosphorylation of Cx43, and 3) possible enhanced phosphorylation of Cx43 in the Golgi |