title: Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.
abstract: Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible that they may influence other cellular mechanisms responsible for proper electrical behaviour of native cardiomyocytes.
authors.affiliation: Copenhagen Heart Arrhythmia Research Centre, Panum Institute, University of Copenhagen, Denmark.
authors.forename: Nathalie H
authors.initials: NH
authors.lastname: Nielsen
authors.forename: Bo G
authors.initials: BG
authors.lastname: Winkel
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Kanters
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitt
authors.forename: Jacob
authors.initials: J
authors.lastname: Hofman-Bang
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Jensen
authors.forename: Bo H
authors.initials: BH
authors.lastname: Bentzen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Sigurd
authors.forename: Lars A
authors.initials: LA
authors.lastname: Larsen
authors.forename: Paal S
authors.initials: PS
authors.lastname: Andersen
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.forename: Keld
authors.initials: K
authors.lastname: Kjeldsen
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
mesh_terms: D002478:Cells, Cultured; D002648:Child; D003001:Cloning, Molecular; D004594:Electrophysiology; D005260:Female; D006323:Heart Arrest / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000473:pathology; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D013997:Time Factors
chemical_list: C496981:KCNA5 protein, human; C489622:KCNE1 protein, human; D051666:Kv1.5 Potassium Channel; D024642:Potassium Channels, Voltage-Gated