Biochem Biophys Res Commun 2007 Dec 28;3644:889-95. doi: 10.1016/j.bbrc.2007.10.106.

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

???displayArticle.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.

???displayArticle.pubmedLink??? 17967416
???displayArticle.link??? Biochem Biophys Res Commun


Species referenced: Xenopus laevis
Genes referenced: kcnj3 kcnj5