کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1936251 1050687 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit
چکیده انگلیسی

Kir3.4 and Kir3.1 potassium channel subunits mediate the acetylcholine induced inwardly rectifying current IKACh 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 Gβγ-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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 364, Issue 4, 28 December 2007, Pages 889–895
نویسندگان
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