Cardiac Sodium Channel Nav1.5 Mechanosensitivity is Inhibited by Ranolazine

Abriel, Hugues (2012). Cardiac Sodium Channel Nav1.5 Mechanosensitivity is Inhibited by Ranolazine. Circulation, 125(22), pp. 2681-3. Baltimore, Md.: Lippincott Williams & Wilkins 10.1161/CIRCULATIONAHA.112.110908

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The cardiac action potential (AP) is initiated by the depolarizing inward sodium current (I(Na)). The pore-forming subunit of the cardiac sodium channel, Na(v)1.5, is the main ion channel that conducts I(Na) in cardiac cells. Despite the large number of studies investigating Na(v)1.5, year after year, we are still learning new aspects regarding its roles in normal cardiac function and in diseased states. The clinical relevance of this channel cannot be understated. The cardiac I(Na) is the target of the class 1 anti-arrhythmic drugs(1), which are nowadays less frequently prescribed because of their well-documented pro-arrhythmic properties(2). In addition, since the first description in 1995 by Keating's group(3) of mutations in patients suffering from congenital long QT syndrome (LQTS) type 3, several hundred genetic variants in SCN5A, the gene coding for Na(v)1.5, have been reported and investigated(4). Interestingly, many of these genetic variants have been found in patients with diverse cardiac manifestations(5) such as congenital LQTS type 3, Brugada syndrome, conduction disorders, and more recently, atrial fibrillation and dilated cardiomyopathy. This impressive list underlines the importance of Na(v)1.5 in cardiac pathologies and raises the question about possible unknown roles and regulatory mechanisms of this channel in cardiac cells. Recent studies have provided experimental evidence that the function of Na(v)1.5, among many other described regulatory mechanisms(6), is also modulated by the mechanical stretch of the membrane in which it is embedded(7), thus suggesting that Na(v)1.5, like other ion channels, is "mechanosensitive". What does this mean? (SELECT FULL TEXT TO CONTINUE).

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten

UniBE Contributor:

Abriel, Hugues

ISSN:

0009-7322

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

06 Dec 2013 13:28

Publisher DOI:

10.1161/CIRCULATIONAHA.112.110908

PubMed ID:

22565937

Web of Science ID:

000306974000009

URI:

https://boris.unibe.ch/id/eprint/7536 (FactScience: 212823)

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