Affiliation:
1. Department of Cardiology Jinshan Hospital Fudan University Shanghai China
2. Department of Cardiology Zhongshan Hospital Fudan University Shanghai China
3. Cardiovascular Research Institute of Wuhan University Wuhan China
4. Department of Cardiology Shanghai Chest Hospital Shanghai Jiaotong University Shanghai China
5. Baoshan Branch Ren Ji Hospital School of Medicine Shanghai Jiaotong University Shanghai China
Abstract
AbstractObjectiveTo investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).Methods and resultsRabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 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 (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (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 (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca2+ 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 Smax and inducibility of VA and alternans.ConclusionPKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.