Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes

Autores

  • Andrés Ricardo Pérez-Riera Design of Studies and Scientifi c Writing Laboratory at the ABC School of Medicine, Santo André, São Paulo, Brazil
  • Rodrigo Daminello Raimundo Design of Studies and Scientifi c Writing Laboratory at the ABC School of Medicine, Santo André, São Paulo, Brazil./Pos-doctoral. Program in Molecular and Integrative Physiological Sciences Department of Environmental Health. Harvard T H Chan School of Public Health, Boston, USA.
  • Rodrigo Akira Watanabe Program in Molecular and Integrative Physiological Sciences (MIPS), Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA.
  • José Luiz Figueiredo Design of Studies and Scientifi c Writing Laboratory at the ABC School of Medicine, Santo André, São Paulo, Brazil.
  • Luiz Carlos de Abreu Design of Studies and Scientifi c Writing Laboratory at the ABC School of Medicine, Santo André, São Paulo, Brazil./Visiting Scientist. Department of Environmental Health. Harvard T H Chan School of Public Health, Boston, USA.

DOI:

https://doi.org/10.7322/jhgd.122759

Palavras-chave:

arrhythmia syndromes, action potential, depolarization, cardiac conduction.

Resumo

The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fi bers. From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a signifi cant aspect for the diagnosis and treatment of heart diseases. Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fi bers to their own rhythm. The rate of these (pacemaker) areas could be altered by modifi cations in ions, temperature and especially, the autonomic system. Excitability is a property of the myocardium to react when stimulated. Another electrical property is conductivity, which is characterized by a conduction and activation process, where the action potential, by the all-or-nothing law, travels throughout the heart. Heart relaxation also stands out as an active process, dependent on the energetic output and on specificion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. In the gene mutation aspects that encode the rapid sodium channel (SCN5A gene), this channel is responsible for several phenotypes, such as Brugada syndrome, idiopathic ventricular fibrillation, dilated cardiomyopathy, early repolarization syndrome, familial atrial fibrillation, variant 3 of long QT syndrome, multifocal ectopic ventricular contractions originating in Purkinje arborizations, progressive cardiac conduction defect (Lenègre disease), sudden infant death syndrome, sick sinus syndrome, sudden unexplained nocturnal death syndrome, among other sodium channel alterations with clinical overlapping. Finally, it seems appropriate to consider the “sodium channel syndrome” (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment.

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2016-11-28

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