Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit.
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Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit. / Calloe, Kirstine; Ravn, Lasse Steen; Schmitt, Nicole; Sui, Jin Liang; Duno, Morten; Haunso, Stig; Grunnet, Morten; Svendsen, Jesper Hastrup; Olesen, Søren-Peter.
In: Biochemical and Biophysical Research Communications, Vol. 364, No. 4, 2007, p. 889-95.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit.
AU - Calloe, Kirstine
AU - Ravn, Lasse Steen
AU - Schmitt, Nicole
AU - Sui, Jin Liang
AU - Duno, Morten
AU - Haunso, Stig
AU - Grunnet, Morten
AU - Svendsen, Jesper Hastrup
AU - Olesen, Søren-Peter
N1 - 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
PY - 2007
Y1 - 2007
N2 - 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
AB - 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
U2 - 10.1016/j.bbrc.2007.10.106
DO - 10.1016/j.bbrc.2007.10.106
M3 - Journal article
C2 - 17967416
VL - 364
SP - 889
EP - 895
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
ID: 2983063