Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG).
Cardiovasc Res
; 59(3): 603-11, 2003 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-14499861
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Long QT Syndrome
/
Potassium Channels
/
Trans-Activators
/
Potassium Channels, Voltage-Gated
/
Cation Transport Proteins
/
DNA-Binding Proteins
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cardiovasc Res
Year:
2003
Document type:
Article
Affiliation country:
Finland