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Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy

  • Experimental Therapeutics (L Maier, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of review

Over the last years, evidence is accumulating that enhanced late sodium current (INaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible therapeutic approach.

Recent Findings

Inhibition of enhanced INaL, e.g., by ranolazine, was shown to reverse these effects in different myocardial diseases including heart failure. The antianginal drug ranolazine has already been examined in larger clinical trials with promising antiarrhythmic actions.

Summary

Enhanced INaL was found to be present in several cardiac pathologies like ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In settings of enhanced INaL, a sodium-dependent calcium overload leads to severe impairment of excitation-contraction coupling and therefore has a high proarrhythmogenic potential. Experimental data showed that inhibition of INaL has a high antiarrhythmic potential which could be confirmed in further clinical trials.

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Acknowledgements

PB is supported by a clinical researcher grant by the College of Translational Medicine of the Ministry for Science and Culture, State of Lower Saxony; SA is funded by the Marga and Walter Boll Foundation; STS is also funded by the Marga and Walter Boll Foundation and the German Center for Cardiovascular Research (DZHK).

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Authors and Affiliations

  1. Clinic for Cardiology and Pneumology/Heart Center, University Medical Center Goettingen, DZHK (German Centre for Cardiovascular Research), Goettingen, Germany

    Philipp Bengel, Shakil Ahmad & Samuel Sossalla

  2. Department for Internal Medicine II, Cardiology, Pneumology, Intensive Care, University Hospital Regensburg, Regensburg, Germany

    Shakil Ahmad & Samuel Sossalla

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  1. Philipp Bengel
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  2. Shakil Ahmad
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  3. Samuel Sossalla
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Correspondence to Samuel Sossalla.

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Philipp Bengel and Shakil Ahmad each declare no potential conflicts of interest.

Samuel Sossalla receives speaker’s honoraria from Berlin-Chemie & Menarini (provider of ranolazine).

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Experimental Therapeutics

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Bengel, P., Ahmad, S. & Sossalla, S. Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy. Curr Heart Fail Rep 14, 179–186 (2017). https://doi.org/10.1007/s11897-017-0333-0

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