Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit.
Research output: Contribution to journal › Journal article › Research › peer-review
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
Udgivelsesdato: 2007-Dec-28
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 364 |
Issue number | 4 |
Pages (from-to) | 889-95 |
Number of pages | 6 |
ISSN | 0006-291X |
DOIs | |
Publication status | Published - 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