@article{oai:niigata-u.repo.nii.ac.jp:00002051,
 author = {Hosaka, Yukio and Hanawa, Haruo and Washizuka, Takashi and Chinushi, Masaomi and Yamashita, Fumio and Yoshida, Tsuyoshi and Komura, Satoru and Watanabe, Hiroshi and Aizawa, Yoshifusa},
 issue = {4},
 journal = {Journal of Molecular and Cellular Cardiology, Journal of Molecular and Cellular Cardiology},
 month = {Apr},
 note = {Andersen’s syndrome, which is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features, is 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 Andersen’s syndrome, 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.},
 pages = {409--415},
 title = {Function, Subcellular Localization and Assembly of a Novel Mutation of KCNJ2 in Andersen's Syndrome},
 volume = {35},
 year = {2003}
}