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Role of Late Sodium Current During Repolarization and Its Pathophysiology

  • Mohamed ChahineEmail author
Chapter

Abstract

Voltage-gated Na channels produce the rapid upstroke of the action potential and are critical elements for maintaining electrical excitability and assuring the coordination of excitation-contraction coupling in the heart. During their activity, these channels cycle between three processes: closing, activation, and inactivation. There is much evidence for the existence of additional channel conformations, modal gating, for instance. The existence of these modes has been observed in cardiac sodium channels. It, therefore, is an intrinsic property of these channels that is in some way related to their proper function. The model gating is thought to underlie the persistent activity of these channels known as late sodium current. Therefore, sodium channels are also involved in determining the duration of action potentials. Excessive residency of sodium channels in a slow mode of gating increases the late sodium current and causes an increase in intracellular sodium and may result in calcium overload and early afterdepolarizations which are substrates for myocyte abnormal electrical activity. This abnormal sodium activity has been found in different pathologies such as type 3 long QT syndrome or heart failure. Ranolazine, an antianginal and a well-tolerated drug, exhibited some beneficial effects in reducing late sodium channel currents and exhibited beneficial effect in animal models of heart failure and proven to be beneficial in several clinical trials.

Keywords

Heart Voltage-gated sodium channels Nav1.5 Late sodium current Persistent sodium current Ranolazine Antiarrhythmic drugs Heart failure Long QT syndrome Cardiac repolarization 

Notes

Acknowledgments

Supported by the Canadian Institutes of Health Research (MOP-111072 and MOP-130373 to MC). Association Française contre les Myopathies (AFM) – Téléthon (Research Grant AFM19962 to MC).

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.CERVO Research Center, Institut Universitaire en Santé Mentale de QuébecQuebec CityCanada
  2. 2.Department of MedicineUniversité LavalQuebec CityCanada

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