K+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation

Colleen E Clancy, Junko Kurokawa, Michihiro Tateyama, Xander H T Wehrens, Robert S. Kass

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Pharmacological intervention, often for the purpose of treating syndromes unrelated to cardiac disease, can increase the vulnerability of some patients to life-threatening rhythm disturbances. This may be due to an underlying propensity stemming from genetic defects or polymorphisms, or structural abnormalities that provide a substrate allowing for the initiation of arrhythmic triggers. A number of pharmacological agents that have proven 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 QT interval on the electrocardiogram. Understanding the structural determinants of K+ channel blockade may 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.

Original languageEnglish (US)
Pages (from-to)441-461
Number of pages21
JournalAnnual Review of Pharmacology and Toxicology
Volume43
DOIs
StatePublished - 2003
Externally publishedYes

Keywords

  • Abnormal repolarization
  • Arrhythmia
  • I
  • I
  • K channel block

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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