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dc.contributor.authorIsik, Turkerja
dc.contributor.authorTakeru, Makiyamaja
dc.contributor.authorMatteo, Vattaja
dc.contributor.authorHideki, Itohja
dc.contributor.authorTakeshi, Ueyamaja
dc.contributor.authorAkihiko, Shimizuja
dc.contributor.authorTomohiko, Aija
dc.contributor.authorMinoru, Horieja
dc.contributor.alternative牧山, 武ja
dc.description.abstractBackground: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. Objective: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. Methods: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study. Genetic screening using direct sequencing identified a novel SCN5A variant, p. V1328M. Electrophysiological parameters of WT and p.V1328M and their effects on drug pharmacokinetics were studied using the patch-clamp method. Results: Whole-cell sodium current densities were similar for WT and p.V1328M channels. While p. V1328M mutation did not affect the voltage-dependence of the activation kinetics, it caused a positive shift of voltage-dependent steady-state inactivation by 7 mV. The tonic block in the presence of pilsicainide was similar in WT and p.V1328M, when sodium currents were induced by a low frequency pulse protocol (q15s). On the contrary, p.V1328M mutation enhanced pilsicainide induced use-dependent block at 2 Hz. (Ki: WT, 35.8 μM; V1328M, 19.3 μM). Conclusion: Our study suggests that a subclinical SCN5A mutation, p.V1328M, might predispose individuals harboring it to drug-induced Brugada Syndrome.ja
dc.publisherPublic Library of Scienceja
dc.rights© 2016 Turker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ja
dc.titleA novel SCN5A mutation associated with drug induced Brugada type ECGja
dc.type.niitypeJournal Articleja
dc.identifier.jtitlePLOS ONEja
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