Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit.

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Kir3.4 and Kir3.1 potassium channel subunits mediate the acetylcholine induced inwardly rectifying current I(KACh) in the heart. We found a glycine to arginine substitution in codon 247 of Kir3.4 in a patient with a single episode of atrial fibrillation (AF). Expression in Xenopus laevis oocytes and two-electrode voltage-clamp revealed that Kir3.4-G247R basal current was reduced compared to wild-type Kir3.4 and co-expression with the muscarinic acetylcholine receptor type 2 showed that also the acetylcholine induced current was severely reduced in Kir3.4-G247R, indicating that the mutation interfered with activation by the stimulatory G betagamma-subunits. Co-expression of Kir3.4-G247R with wild-type Kir3.4 or Kir3.1 had a compensating effect on both basal current levels and the response to muscarinic stimulation suggesting the function of Kir3.4-G247R is compensated in vivo. This may explain the lack of clear clinical manifestations and further studies are necessary to elucidate if mutations in Kir3.4 are predisposing AF.
Udgivelsesdato: 2007-Dec-28
Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Issue number4
Pages (from-to)889-95
Number of pages6
Publication statusPublished - 2007

Bibliographical note

Keywords: Animals; Atrial Fibrillation; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Ion Channel Gating; Mutagenesis, Site-Directed; Mutation; Oocytes; Potassium; Structure-Activity Relationship; Xenopus laevis

ID: 2983063