Referenced in: none

Automatically associated channels: Kir2.1

Title: Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome.

Authors: Yukio Hosaka, Haruo Hanawa, Takashi Washizuka, Masaomi Chinushi, Fumio Yamashita, Tsuyoshi Yoshida, Satoru Komura, Hiroshi Watanabe, Yoshifusa Aizawa

Journal, date & volume: J. Mol. Cell. Cardiol., 2003 Apr , 35, 409-15

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12689820

Abstract
Andersen's syndrome (AS) (which is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features), a hereditary disease, and missense mutations of KCNJ2 (which encodes an inward rectifying potassium channel) have been reported recently. We performed clinical and molecular analyses of a patient with AS, and found a novel mutation (G215D) of KCNJ2. Twelve-lead electrocardiography revealed a long QT interval and frequent premature ventricular contractions, and polymorphic ventricular tachycardia was induced by programmed electrical stimulation. Use of a conventional whole-cell patch-clamp system with COS7 cells demonstrated that the G215D mutant was non-functional, and that co-expression of wild type (WT)- and mutant-KCNJ2 shows a dominant negative effect on both inward and outward currents. We performed confocal laser scanning microscopy to assess the cellular trafficking of WT- and mutant-KCNJ2 subunits tagged with yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP), respectively. Tagging with the YFP did not affect the channel function of WT-KCNJ2 and both proteins showed similar plasma membrane fluorescence patterns. Furthermore, the result of fluorescence resonance energy transfer (FRET) studies at the plasma membrane region suggested that both YFP-tagged WT- and CFP-tagged mutant-KCNJ2 combine to construct a hetero-multimer of the potassium channel. In conclusion, the G215D mutant of KCNJ2 is distributed normally in the plasma membrane, but exhibits a dominant-negative effect and reduces the Kir2.1 current, presumably due to hetero-multimer construction.