1. Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG).
- Author
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Paavonen KJ, Chapman H, Laitinen PJ, Fodstad H, Piippo K, Swan H, Toivonen L, Viitasalo M, Kontula K, and Pasternack M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Analysis of Variance, Animals, COS Cells, Cell Line, Child, Child, Preschool, ERG1 Potassium Channel, Electrocardiography, Ether-A-Go-Go Potassium Channels, Exercise Test, Female, Gene Expression, Heterozygote, Humans, Kidney, Long QT Syndrome physiopathology, Male, Middle Aged, Patch-Clamp Techniques, Potassium Channels metabolism, Transcriptional Regulator ERG, Transfection, Cation Transport Proteins, DNA-Binding Proteins, Long QT Syndrome metabolism, Polymorphism, Genetic, Potassium Channels genetics, Potassium Channels, Voltage-Gated, Trans-Activators
- Abstract
Objective: To determine whether the amino acid 897 threonine (T) to lysine (K) polymorphism of the KCNH2 (HERG) potassium channel influences channel performance or patient phenotype., Methods: The phenotypic effects of this polymorphism were investigated in vitro by electrophysiological experiments in HEK-293 cells and in vivo by exercise electrocardiography in a group of LQTS patients carrying the same genetically proven KCNQ1 mutation., Results: When expressed in HEK-293 cells, the 897T isoform of the KCNH2 channel exhibited changes in inactivation and deactivation properties, and a smaller current density than the more common 897K isoform. Western blot experiments indicated that the decreased current density associated with 897T was caused by reduced channel expression. During a maximal exercise test in 39 LQT1 patients carrying an identical KCNQ1 mutation (G589D) and showing a prolonged QT interval (>440 ms), QT intervals were longer in patients carrying the 897T allele than in those homozygous for the 897K allele., Conclusions: The K897T variation has an effect on channel function and clinical phenotype. Our data warrant further investigations into the significance of this polymorphism in drug-induced and inherited LQTS.
- Published
- 2003
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