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Antiarrhythmics—from cell to clinic: past, present, and future
  1. J C Hancoxa,
  2. K C R Patela,
  3. J V Jonesb
  1. aDepartment of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK, bDepartment of Cardiology, Bristol Royal Infirmary, United Bristol Healthcare Trust, Bristol, UK
  1. Dr Hancox email: jules.hancox{at}

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The past two decades have witnessed a rapid growth in understanding of the cellular and molecular basis of both normal and pathological electrophysiology. Elucidation of cardiac ion channel structure and function has contributed to many of these advances. As a result, we may be on the verge of an era where arrhythmia management will no longer be dominated by trial and error based observational treatment. Our aim in this article is to provide an overview of antiarrhythmic drug action, linking known actions at the level of cellular electrophysiology to clinical use. Taking particular examples, we shall also illustrate how molecular genetic advances have shown that some rhythm disturbances can result from specific defects in genes encoding cardiac ion channels. Making reference to investigational drugs under study, we will also consider the issue of whether advances in the understanding of cardiac cellular electrophysiology may improve rational approaches to antiarrhythmic drug design and treatment.

The mechanism of drug action is central to the process of choosing a drug to treat any particular arrhythmia. Thus it is useful to consider first impulse generation at the cellular level. This in turn demands consideration of the ion channels underpinning impulse generation in different cardiac muscle cell types. It is the opening and closing of a range of different ion channels that leads to the distinct profiles of membrane potential which comprise cardiac action potentials. Therefore, we shall initially consider the electrophysiological characteristics of cardiac action potentials, aspects of ion channel function, and ion channels as sites of antiarrhythmic drug action.

Membrane and action potentials: conventions

Figure 1 shows schematic representations of action potentials from pacemaker, ventricular, and atrial tissues. Whereas the membrane potential in pacemaker cells (typically from the sinus node, as this is usually the dominant pacemaker) constantly cycles (fig 1A), cells (myocytes) from ventricular (fig 1 …

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