Biophysical mechanisms of myocardium sodium channelopathies.

Autor: Zaytseva AK; Almazov National Medical Research Centre, St. Petersburg, Russia. zaytseva.anastasia.zak@gmail.com.; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia. zaytseva.anastasia.zak@gmail.com., Kulichik OE; Almazov National Medical Research Centre, St. Petersburg, Russia., Kostareva AA; Karolinska Institute, Stockholm, Sweden., Zhorov BS; Almazov National Medical Research Centre, St. Petersburg, Russia.; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.; McMaster University, Hamilton, Canada.
Jazyk: angličtina
Zdroj: Pflugers Archiv : European journal of physiology [Pflugers Arch] 2024 May; Vol. 476 (5), pp. 735-753. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1007/s00424-024-02930-3
Abstrakt: Genetic variants of gene SCN5A encoding the alpha-subunit of cardiac voltage-gated sodium channel Na v 1.5 are associated with various diseases, including long QT syndrome (LQT3), Brugada syndrome (BrS1), and progressive cardiac conduction disease (PCCD). In the last decades, the great progress in understanding molecular and biophysical mechanisms of these diseases has been achieved. The LQT3 syndrome is associated with gain-of-function of sodium channels Na v 1.5 due to impaired inactivation, enhanced activation, accelerated recovery from inactivation or the late current appearance. In contrast, BrS1 and PCCD are associated with the Na v 1.5 loss-of-function, which in electrophysiological experiments can be manifested as reduced current density, enhanced fast or slow inactivation, impaired activation, or decelerated recovery from inactivation. Genetic variants associated with congenital arrhythmias can also disturb interactions of the Na v 1.5 channel with different proteins or drugs and cause unexpected reactions to drug administration. Furthermore, mutations can affect post-translational modifications of the channels and their sensitivity to pH and temperature. Here we briefly review the current knowledge on biophysical mechanisms of LQT3, BrS1 and PCCD. We focus on limitations of studies that use heterologous expression systems and induced pluripotent stem cells (iPSC) derived cardiac myocytes and summarize our understanding of genotype-phenotype relations of SCN5A mutations.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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