Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death

Stefan Wagner, Lars S. Maier, Donald M Bers

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1956-1970
Number of pages15
JournalCirculation Research
Volume116
Issue number12
DOIs
StatePublished - Jun 5 2015

Fingerprint

Sudden Cardiac Death
Ion Channels
Tachycardia
Sodium
Calcium
Cardiac Arrhythmias
Heart Failure
Ion Pumps
Calcium-Calmodulin-Dependent Protein Kinases
Ryanodine Receptor Calcium Release Channel
Cardiac Myocytes
Causality
Adenosine Triphosphatases
Cause of Death
Heart Diseases
Homeostasis
Ions
Therapeutics

Keywords

  • alternans
  • arrhythmias
  • calcium
  • calcium/calmodulin-dependent kinase II
  • sodium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death. / Wagner, Stefan; Maier, Lars S.; Bers, Donald M.

In: Circulation Research, Vol. 116, No. 12, 05.06.2015, p. 1956-1970.

Research output: Contribution to journalArticle

Wagner, Stefan ; Maier, Lars S. ; Bers, Donald M. / Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death. In: Circulation Research. 2015 ; Vol. 116, No. 12. pp. 1956-1970.
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