The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Ionic Mechanisms Responsible for the Electrocardiographic Phenotype of the Brugada Syndrome Are Temperature Dependent
Open accessAbstract
Abstract —The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in SCN5A , the gene encoding for the α subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32°C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32°C. Recovery from inactivation was slower for Thr1620Met at 32°C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states.
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Cites
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Self-citationSCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome
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Cited by
Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.178233 · Cited by 1,080
Maron, B. J., Chaitman, B. R., Ackerman, M. J., Bayés de Luna, A., Corrado, D., Crosson, J. E., Deal, B. J., Driscoll, D. J., Estes, N. A. M., Araújo, C. G. S., et al. (2004) · Circulation · doi:10.1161/01.cir.0000128363.85581.e1 · Cited by 591
Self-citationIonic Current Basis of Electrocardiographic Waveforms: A Model Study
Gima, K., & Rudy, Y. (2002) · Circulation Research · doi:10.1161/01.res.0000016960.61087.86 · Cited by 396
Inherited disorders of voltage-gated sodium channels
George, A. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25505 · Cited by 365
Electrical heterogeneity within the ventricular wall
Antzelevitch, C., & Fish, J. (2001) · Basic Research in Cardiology · doi:10.1007/s003950170002 · Cited by 334
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Metadata
- Authors
- Dumaine, R., Towbin, J. A., Brugada, P., Vatta, M., Nesterenko, D. V., Nesterenko, V. V., Brugada, J., Brugada, R., & Antzelevitch, C.
- Venue
- Circulation Research
- Published
- 1999-10-29
- Volume
- 85
- Issue
- 9
- Pages
- 803-809
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2131871260
- Cited by
- 601
- References
- 24
- FWCI
- 17.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dumaine, R., Towbin, J. A., Brugada, P., Vatta, M., Nesterenko, D. V., Nesterenko, V. V., Brugada, J., Brugada, R., & Antzelevitch, C. (1999). Ionic Mechanisms Responsible for the Electrocardiographic Phenotype of the Brugada Syndrome Are Temperature Dependent. Circulation Research. https://doi.org/10.1161/01.res.85.9.803
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