Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current

Abstract Objective To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). Methods and results Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S 1 –S 2 ) method and dynamic S 1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) ( n = 15) greatly steepened the restitution curves ( S max > 1) ( p < .01) at each site compared to the control group ( n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of S max ( p < .05) and decreased the thresholds of the VA and APD alternans ( p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) ( n = 10), reversibly flattened the APD restitution curves at each site ( S max < 1), decreased the spatial dispersions of S max , and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca 2+ current was significantly increased by addition of PMA compared with control (CTL) group ( p < .05). Antagonize this current with verapamil ( n = 10) can fully inhibited the PMA induced increasing of S max and inducibility of VA and alternans. Conclusion PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca 2+ influx.