Structural Determinants of Potassium Channel Blockade and Drug-Induced Arrhythmias

  • X.H.T. Wehrens
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 171)

Abstract

Cardiac K+ channels play an important role in the regulation of the shape and duration of the action potential. They have been recognized as targets for the actions of neurotransmitters, hormones, and anti-arrhythmic drugs that prolong the action potential duration (APD) and increase refractoriness. However, pharmacological therapy, often for the purpose of treating syndromes unrelated to cardiac disease, can also increase the vulnerability of some patients to life-threatening rhythm disturbances. This may be due to an underlying propensity stemming from inherited mutations or polymorphisms, or structural abnormalities that provide a substrate allowing for the initiation of arrhythmic triggers. A number of pharmacological agents that have proved useful in the treatment of allergic reactions, gastrointestinal disorders, and psychotic disorders, among others, have been shown to reduce repolarizing K+ currents and prolong the Q-T interval on the electrocardiogram. Understanding the structural determinants of K+ channel blockade might provide new insights into the mechanism and rate-dependent effects of drugs on cellular physiology. Drug-induced disruption of cellular repolarization underlies electrocardiographic abnormalities that are diagnostic indicators of arrhythmia susceptibility.

Keywords

Potassium channel Arrhythmias Long QT syndrome Delayed rectifier Repolarization 
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© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • X.H.T. Wehrens
    • 1
  1. 1.Center for Molecular Cardiology, Dept. of Physiology and Cellular BiophysicsCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA

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