Role of sodium and calcium dysregulation in tachyarrhythmias in sudden cardiac death.

Abstract:

:Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger, and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin-dependent protein kinase and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachyarrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like heart failure.

journal_name

Circ Res

journal_title

Circulation research

authors

Wagner S,Maier LS,Bers DM

doi

10.1161/CIRCRESAHA.116.304678

subject

Has Abstract

pub_date

2015-06-05 00:00:00

pages

1956-70

issue

12

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.116.304678

journal_volume

116

pub_type

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