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The Role of Cellular Sodium and Calcium Loading in Cardiac Energetics and Arrhythmogenesis: Contribution of the Late Sodium Current

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Electrical Diseases of the Heart

Abstract

An imbalance between myocardial oxygen supply and demand, as occurs during ischemia, leads to increases of cellular concentrations of sodium and calcium (Figure 8-1).1 Reperfusion of the ischemic heart may further exacerbate an ischemia-induced loss of ionic homeostasis. Ischemia and ischemic metabolites can increase the influx of sodium into myocytes.2–7 Concurrent reduction of sodium efflux during ischemia, as a consequence of reductions of cellular ATP and activity of the cell membrane Na+-K+-ATPase, allows the intracellular sodium concentration to rise. By virtue of the coupled exchange of sodium and calcium facilitated by the cell membrane Na+-Ca2+ exchanger (NCX), an elevation of the intracellular sodium concentration leads to an increased influx of calcium. An excessive or prolonged increase of the intracellular sodium concentration leads to intracellular calcium ([Ca2+]i) overload. The mechanisms and consequences of sodium and calcium overload are the subject of this review. Evidence supporting a role for the late sodium current (late I Na) as a mechanism of calcium overloading and cardiac dysfunction is emphasized.

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Authors and Affiliations

  1. Department of Pharmacology, CV Therapeutics, Inc., Palo Alto, CA, USA

    John C. Shryock PhD (Senior Director) & Sridharan Rajamani PhD (Scientist)

  2. CV Therapeutics, Inc., Palo Alto, CA, USA

    Luiz Belardinelli MD (Senior Vice-President of Pharmacology and Translational Biomedical Research)

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Editors and Affiliations

  1. Cardiovascular Boehringer Ingelheim Pharmaceuticals Ridgefield, CT, USA

    Ihor Gussak MD, PhD, FACC (Deputy Therapeutic Area Head, Professor of Pharmacology) (Deputy Therapeutic Area Head, Professor of Pharmacology)

  2. Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Bridgewater, NJ, USA

    Ihor Gussak MD, PhD, FACC (Deputy Therapeutic Area Head, Professor of Pharmacology) (Deputy Therapeutic Area Head, Professor of Pharmacology)

  3. Gordon K. Moe Scholar Masonic Medical Research Laboratory, Utica, NY, USA

    Charles Antzelevitch PhD, FACC, FAHA, FHRS (Executive Director and Director of Research) (Executive Director and Director of Research)

  4. Upstate Medical University, Syracuse, NY, USA

    Charles Antzelevitch PhD, FACC, FAHA, FHRS (Executive Director and Director of Research) (Executive Director and Director of Research)

  5. Heart Failure Research Center Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands

    Arthur A. M. Wilde MD, PhD, FESC, FAHA (Professor) (Professor)

  6. Mayo Clinic College of Medicine, Rochester, MN, USA

    Paul A. Friedman MD (Professor of Medicine) & Michael J. Ackerman MD, PhD, FACC (Professor of Medicine, Pediatrics and Pharmacology, Consultant Cardiovascular Disease and Pediatric Cardiology, Director Long QT Syndrome Clinic and the Mayo Clinic Windland Smith Rice Sudden Death Genomics) (Professor of Medicine) &  (Professor of Medicine, Pediatrics and Pharmacology, Consultant Cardiovascular Disease and Pediatric Cardiology, Director Long QT Syndrome Clinic and the Mayo Clinic Windland Smith Rice Sudden Death Genomics)

  7. Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA

    Win-Kuang Shen MD (Consultant, Professor of Medicine) (Consultant, Professor of Medicine)

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Shryock, J.C., Belardinelli, L., Rajamani, S. (2008). The Role of Cellular Sodium and Calcium Loading in Cardiac Energetics and Arrhythmogenesis: Contribution of the Late Sodium Current. In: Gussak, I., Antzelevitch, C., Wilde, A.A.M., Friedman, P.A., Ackerman, M.J., Shen, WK. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-84628-854-8_9

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