PMID- 27459728 OWN - NLM STAT- MEDLINE DCOM- 20171109 LR - 20181020 IS - 1748-1716 (Electronic) IS - 1748-1708 (Linking) VI - 219 IP - 3 DP - 2017 Mar TI - Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice. PG - 660-668 LID - 10.1111/apha.12761 [doi] AB - AIM: In this study, we investigate the impact of altered action potential durations (APD) on ventricular repolarization time and proarrhythmia in mice with and without genetic deletion of the K(+) -channel-interacting protein 2 (KChIP2(-/-) and WT respectively). Moreover, we examine the interrelationship between the dispersion of repolarization time and current pulse amplitude in provoking ventricular arrhythmia. METHODS: Intracardiac pacing in anesthetized mice determined refractory periods and proarrhythmia susceptibility. Regional activation time (AT), APD and repolarization time (=AT + APD) were measured in isolated hearts using floating microelectrodes. RESULTS: Proarrhythmia in WT and KChIP2(-/-) was not sensitive to changes in refractory periods. Action potentials were longer in KChIP2(-/-) hearts compared to WT hearts. Isolated WT hearts had large apico-basal dispersion of repolarization time, whereas hearts from KChIP2(-/-) mice had large left-to-right ventricular dispersion of repolarization time. Pacing from the right ventricle in KChIP2(-/-) mice in vivo revealed significant lower current pulse amplitudes needed to induce arrhythmias in these mice. CONCLUSION: Large heterogeneity of repolarization time is proarrhythmic when pacing is delivered from the location of earlier repolarization time. Ventricular repolarization time, location of the pacing stimulus and the amplitude of the stimulating current pulse are critical parameters underlying arrhythmia vulnerability. CI - (c) 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. FAU - Speerschneider, T AU - Speerschneider T AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Grubb, S AU - Grubb S AD - Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Olesen, S P AU - Olesen SP AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Calloe, K AU - Calloe K AD - Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Thomsen, M B AU - Thomsen MB AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160824 PL - England TA - Acta Physiol (Oxf) JT - Acta physiologica (Oxford, England) JID - 101262545 RN - 0 (Kcnip2 protein, mouse) RN - 0 (Kv Channel-Interacting Proteins) SB - IM MH - Action Potentials/*physiology MH - Animals MH - Arrhythmias, Cardiac/metabolism/*physiopathology MH - Disease Models, Animal MH - Electrophysiology MH - Heart Ventricles/*physiopathology MH - Kv Channel-Interacting Proteins/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout OTO - NOTNLM OT - KChIP2 OT - dispersion of action potential duration OT - fibrillation threshold OT - floating microelectrode technique OT - proarrhythmia mechanisms EDAT- 2016/07/28 06:00 MHDA- 2017/11/10 06:00 CRDT- 2016/07/27 06:00 PHST- 2016/04/01 00:00 [received] PHST- 2016/04/13 00:00 [revised] PHST- 2016/07/11 00:00 [revised] PHST- 2016/07/22 00:00 [accepted] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/11/10 06:00 [medline] PHST- 2016/07/27 06:00 [entrez] AID - 10.1111/apha.12761 [doi] PST - ppublish SO - Acta Physiol (Oxf). 2017 Mar;219(3):660-668. doi: 10.1111/apha.12761. Epub 2016 Aug 24.