K+ channel structure-activity relationships and mechanisms of drug-induced QT prolongation.
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.
Clancy
Colleen E
CE
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. cc2114@columbia.edu
Kurokawa
Junko
J
Tateyama
Michihiro
M
Wehrens
Xander H T
XH
Kass
Robert S
RS
D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D026902:Potassium Channel Blockers / Q000009:adverse effects*; D015221:Potassium Channels / Q000737:chemistry*; D013329:Structure-Activity Relationship
D026902:Potassium Channel Blockers; D015221:Potassium Channels