Referenced in: Kir3.4

Automatically associated channels: Kir3.1 , Kir3.4

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

Authors: Kirstine Calloe, Lasse Steen Ravn, Nicole Schmitt, Jin Liang Sui, Morten Duno, Stig Haunso, Morten Grunnet, Jesper Hastrup Svendsen, Soren-Peter Olesen

Journal, date & volume: Biochem. Biophys. Res. Commun., 2007 Dec 28 , 364, 889-95

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17967416

Abstract
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.