Lidocaine-induced brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel
dc.contributor | Barajas-Martínez, H.M., Masonic Medical Research Laboratory, Utica, NY, United States, South University Center, Cd. Guzman, Mexico, University of Guadalajara, Cd. Guzman, Mexico, Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue, Sherbrooke, QC, Canada; Hu, D., Masonic Medical Research Laboratory, Utica, NY, United States, RenMin Hospital, WuHan University, HuBei, China; Cordeiro, J.M., Masonic Medical Research Laboratory, Utica, NY, United States; Wu, Y., Masonic Medical Research Laboratory, Utica, NY, United States; Kovacs, R.J., Krannert Institute of Cardiology, Indianapolis, IN, United States; Meltser, H., Krannert Institute of Cardiology, Indianapolis, IN, United States; Kui, H., Second Affiliated Hospital of Nanchang University, Jiangxi of China, China; Elena, B., Masonic Medical Research Laboratory, Utica, NY, United States; Brugada, R., Montreal Heart Institute, University of Montréal, Montreal, QC, Canada; Antzelevitch, C., Masonic Medical Research Laboratory, Utica, NY, United States; Dumaine, R., Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue, Sherbrooke, QC, Canada | |
dc.creator | Barajas-Martinez, H.M. | |
dc.creator | Hu, D. | |
dc.creator | Cordeiro, J.M. | |
dc.creator | Wu, Y. | |
dc.creator | Kovacs, R.J. | |
dc.creator | Meltser, H. | |
dc.creator | Kui, H. | |
dc.creator | Elena, B. | |
dc.creator | Brugada, R. | |
dc.creator | Antzelevitch, C. | |
dc.creator | Dumaine, R. | |
dc.date.accessioned | 2015-11-19T18:50:49Z | |
dc.date.accessioned | 2023-07-03T23:36:51Z | |
dc.date.available | 2015-11-19T18:50:49Z | |
dc.date.available | 2023-07-03T23:36:51Z | |
dc.date.created | 2015-11-19T18:50:49Z | |
dc.date.issued | 2008 | |
dc.identifier | http://hdl.handle.net/20.500.12104/65915 | |
dc.identifier | 10.1161/CIRCRESAHA.108.172619 | |
dc.identifier | http://www.scopus.com/inward/record.url?eid=2-s2.0-50949092654&partnerID=40&md5=44df12f00203be4d16925ea516e0938c | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/7250269 | |
dc.description.abstract | Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been shown to exert no effect in patients with Brugada syndrome. We characterized a novel double mutation of SCN5A (V232I in DI-S4+L1308F in DIII-S4) identified in a rare case of lidocaine (1 mg/kg)-induced Brugada syndrome. We studied lidocaine blockade of INa generated by wild-type and V232I+L1308F mutant cardiac sodium channels expressed in mammalian TSA201 cells using patch clamp techniques. Despite no significant difference in steady-state gating parameters between V232I+L1308F and wild-type sodium currents at baseline, use-dependent inhibition of INa by lidocaine was more pronounced in V232I+L1308F versus wild-type (73.0±0.1% versus 18.23±0.04% at 10 μmol/L measured at 10 Hz, respectively). A dose of 10 μmol/L lidocaine also caused a more negative shift of steady-state inactivation in V232I+L1308F versus wild-type (-14.1±0.3 mV and -4.8±0.3 mV, respectively). The individual mutations produced a much less accentuated effect. We report the first case of lidocaine-induced Brugada electrocardiogram phenotype. The double mutation in SCN5A, V232I, and L1308F alters the affinity of the cardiac sodium channel for lidocaine such that the drug assumes Class IC characteristics with potent use-dependent block of the sodium channel. Our results demonstrate an additive effect of the 2 missense mutations to sensitize the sodium channel to lidocaine. These findings suggest caution when treating patients carrying such genetic variations with Class I antiarrhythmic drugs. © 2008 American Heart Association, Inc. | |
dc.relation | Circulation Research | |
dc.relation | 103 | |
dc.relation | 4 | |
dc.relation | 396 | |
dc.relation | 404 | |
dc.relation | Scopus | |
dc.relation | WOS | |
dc.title | Lidocaine-induced brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel | |
dc.type | Article |