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

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

SN - 0006-291X

VL - 364

SP - 889

EP - 895

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -