Sodium calcium exchange as a target for antiarrhythmic therapy

K. R. Sipido, A. Varro, D. Eisner

Research output: Chapter in Book/Report/Conference proceedingChapter

39 Citations (Scopus)

Abstract

In search of better antiarrhythmic therapy, targeting the Na/Ca exchanger is an option to be explored. The rationale is that increased activity of the Na/Ca exchanger has been implicated in arrhythmogenesis in a number of conditions. The evidence is strong for triggered arrhythmias related to Ca 2+ overload, due to increased Na+ load or during adrenergic stimulation; the Na/Ca exchanger may be important in triggered arrhythmias in heart failure and in atrial fibrillation. There is also evidence for a less direct role of the Na/Ca exchanger in contributing to remodelling processes. In this chapter, we review this evidence and discuss the consequences of inhibition of Na/Ca exchange in the perspective of its physiological role in Ca2+ homeostasis. We summarize the current data on the use of available blockers of Na/Ca exchange and propose a framework for further study and development of such drugs. Very selective agents have great potential as tools for further study of the role the Na/Ca exchanger plays in arrhythmogenesis. For therapy, they may have their specific indications, but they carry the risk of increasing Ca2+ load of the cell. Agentswith a broader action that includes Ca2+ channel blockmay have advantages in other conditions, e.g. with Ca2+ overload. Additional actions such as block of K+ channels, which may be unwanted in e.g. heart failure, may be used to advantage as well.

Original languageEnglish
Title of host publicationBasis and Treatment of Cardiac Arrhythmias
EditorsRobert S. Kass, Colleen E. Clancy
Pages159-199
Number of pages41
DOIs
Publication statusPublished - Dec 1 2006

Publication series

NameHandbook of Experimental Pharmacology
Volume171
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • Afterdepolarizations
  • Arrhythmias
  • Heart failure
  • Sarcoplasmic reticulum
  • Sodium/calcium exchange

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Sipido, K. R., Varro, A., & Eisner, D. (2006). Sodium calcium exchange as a target for antiarrhythmic therapy. In R. S. Kass, & C. E. Clancy (Eds.), Basis and Treatment of Cardiac Arrhythmias (pp. 159-199). (Handbook of Experimental Pharmacology; Vol. 171). https://doi.org/10.1007/3-540-29715-4-6