{"id":39,"date":"2020-05-25T16:38:17","date_gmt":"2020-05-25T07:38:17","guid":{"rendered":"https:\/\/gucvmed.med.gunma-u.ac.jp\/0_web\/?page_id=39"},"modified":"2025-04-09T10:21:46","modified_gmt":"2025-04-09T01:21:46","slug":"%e3%83%88%e3%83%a9%e3%83%b3%e3%82%b9%e3%83%ac%e3%83%bc%e3%82%b7%e3%83%a7%e3%83%8a%e3%83%ab%e3%83%bb-%e3%83%aa%e3%82%b5%e3%83%bc%e3%83%81%e9%83%a8%e9%96%80","status":"publish","type":"page","link":"https:\/\/gucvmed.med.gunma-u.ac.jp\/?page_id=39","title":{"rendered":"\u30c8\u30e9\u30f3\u30b9\u30ec\u30fc\u30b7\u30e7\u30ca\u30eb\u30fb \u30ea\u30b5\u30fc\u30c1\u90e8\u9580"},"content":{"rendered":"<section>\n<h4>\u90e8\u9580\u306e\u7d39\u4ecb<\/h4>\n<p>\u5f53\u79d1\u3067\u306f\u3001\u7fa4\u99ac\u5927\u5b66\u4eba\u3092\u5bfe\u8c61\u3068\u3059\u308b\u533b\u5b66\u7cfb\u7814\u7a76\u502b\u7406\u5be9\u67fb\u59d4\u54e1\u4f1a\u306e\u627f\u8a8d\u3092\u5f97\u3066\u3001\u907a\u4f1d\u6027\u5faa\u74b0\u5668\u75be\u60a3\u306e\u4e2d\u3067\u4e3b\u306b\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u30fb\u5fc3\u7b4b\u75c7\uff08\u907a\u4f1d\u6027QT\u5ef6\u9577\u75c7\u5019\u7fa4\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3001\u30ab\u30c6\u30b3\u30e9\u30df\u30f3\u8a98\u767a\u6027\u591a\u5f62\u6027\u5fc3\u5ba4\u983b\u62cd\u3001\u4e0d\u6574\u8108\u6e90\u6027\u53f3\u5ba4\u5fc3\u7b4b\u75c7\u306a\u3069\uff09\u306e\u907a\u4f1d\u5b50\u89e3\u6790\u3092\u65bd\u884c\u3057\u3066\u304a\u308a\u307e\u3059\u3002<br \/>\n\u6211\u3005\u306e\u7814\u7a76\u306e\u76ee\u7684\u306f\u3001\u2460\u75be\u60a3\u306e\u539f\u56e0\u3068\u306a\u308b\u907a\u4f1d\u5b50\u5909\u7570\u30fb\u591a\u578b\u3092\u540c\u5b9a\u3057\u3001\u2461\u907a\u4f1d\u5b50\u5909\u7570\u30fb\u591a\u578b\u306b\u3088\u308a\u75be\u60a3\u3092\u767a\u75c7\u3059\u308b\u30e1\u30ab\u30cb\u30ba\u30e0\u3001\u75be\u60a3\u306e\u5206\u5b50\u75c5\u614b\u3092\u89e3\u660e\u3057\u3001\u3055\u3089\u306b\u3001\u2462\u5f97\u3089\u308c\u305f\u77e5\u898b\u3092\u5b9f\u5730\u8a3a\u7642\u306b\u751f\u304b\u3059\u3053\u3068\u3067\u3059\u3002\u6211\u3005\u306e\u7814\u7a76\u306f\u5c0f\u898f\u6a21\u3067\u306f\u3042\u308a\u307e\u3059\u304c\u3001\u5730\u57df\u306b\u6839\u3056\u3057\u3066\u304a\u308a\u3001\u60a3\u8005\u69d8\u304b\u3089\u5f97\u3089\u308c\u305f\u907a\u4f1d\u60c5\u5831\u3092\u5b9f\u5730\u8a3a\u7642\u306b\u304a\u3044\u3066\u60a3\u8005\u69d8\u306b\u6700\u5927\u9650\u306b\u9084\u5143\u3059\u308b\u533b\u7642\u3092\u5b9f\u8df5\u3057\u3066\u304a\u308a\u307e\u3059\u3002\u6211\u3005\u306f\u3053\u308c\u307e\u3067\u306b\u3001\u907a\u4f1d\u6027QT\u5ef6\u9577\u75c7\u5019\u7fa4\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3001\u30ab\u30c6\u30b3\u30e9\u30df\u30f3\u8a98\u767a\u6027\u591a\u5f62\u6027\u5fc3\u5ba4\u983b\u62cd\u3001\u4e0d\u6574\u8108\u6e90\u6027\u53f3\u5ba4\u5fc3\u7b4b\u75c7\u7b49\u306b\u304a\u3044\u3066\u3001\u65b0\u898f\u5909\u7570\u3092\u542b\u3080\u591a\u304f\u306e\u5909\u7570\u3092\u540c\u5b9a\u3057\u3001\u81e8\u5e8a\u50cf\u3092\u89e3\u6790\u3057\u3001\u3055\u3089\u306b\u5909\u7570\u907a\u4f1d\u5b50\u306e\u6a5f\u80fd\u7570\u5e38\u3092\u89e3\u660e\u3059\u308b\u3053\u3068\u306b\u3088\u308a\u5f97\u3089\u308c\u305f\u591a\u304f\u306e\u60c5\u5831\u3092\u767a\u4fe1\u3057\u3066\u304d\u307e\u3057\u305f\u3002\u6211\u3005\u306e\u7814\u7a76\u6210\u679c\u306f\u3001\u75be\u60a3\u306e\u5206\u5b50\u75c5\u614b\u3092\u89e3\u660e\u3057\u3001\u81f4\u6b7b\u6027\u4e0d\u6574\u8108\u767a\u75c7\u306e\u4e88\u77e5\u30fb\u30ea\u30b9\u30af\u5c64\u5225\u5316\u3092\u53ef\u80fd\u3068\u3057\u3001\u7a81\u7136\u6b7b\u4e88\u9632\u306b\u3064\u306a\u304c\u308b\u3082\u306e\u3068\u78ba\u4fe1\u3057\u3066\u304a\u308a\u307e\u3059\u3002<br \/>\n\u907a\u4f1d\u6027\u5faa\u74b0\u5668\u75be\u60a3\u3068\u8a3a\u65ad\u3055\u308c\u308b\u60a3\u8005\u69d8\u306e\u6570\u306f\u5e74\u3005\u5897\u52a0\u3057\u3066\u304a\u308a\u3001\u5faa\u74b0\u5668\u75be\u60a3\u306e\u8a3a\u7642\u306b\u304a\u3044\u3066\u907a\u4f1d\u5b50\u8a3a\u65ad\/\u8a3a\u7642\u306f\u3001\u4eca\u5f8c\u307e\u3059\u307e\u3059\u91cd\u8981\u306b\u306a\u308b\u3068\u8003\u3048\u3089\u308c\u307e\u3059\u3002\u540c\u6642\u306b\u3001\u907a\u4f1d\u5b50\u8a3a\u65ad\/\u8a3a\u7642\u306f\u300c\u907a\u4f1d\u6027\u300d\u3067\u3042\u308b\u304c\u6545\u3001\u502b\u7406\u9762\u3092\u542b\u3081\u69d8\u3005\u306a\u554f\u984c\u3092\u591a\u304f\u6709\u3057\u3066\u304a\u308a\u3001\u60a3\u8005\u69d8\u306e\u7cbe\u795e\u7684\u30b1\u30a2\u3082\u3068\u3066\u3082\u91cd\u8981\u3067\u3059\u3002\u6211\u3005\u306f\u3001\u60a3\u8005\u69d8\u306b\u30a8\u30d3\u30c7\u30f3\u30b9\u306b\u57fa\u3065\u304f\u6700\u5148\u7aef\u306e\u533b\u7642\u3092\u63d0\u4f9b\u3057\u3066\u3044\u304f\u3068\u3068\u3082\u306b\u3001\u533b\u5e2b\u3001\u30d1\u30e9\u30e1\u30c7\u30a3\u30ab\u30eb\u3001\u907a\u4f1d\u5b50\u8a3a\u7642\u90e8\u304c\u9023\u643a\u3057\u3001\u907a\u4f1d\u6027\u75be\u60a3\u8a3a\u7642\u304c\u304b\u304b\u3048\u308b\u8ab2\u984c\u3092\u5c11\u3057\u3067\u3082\u514b\u670d\u3067\u304d\u308b\u8a3a\u7642\u30b7\u30b9\u30c6\u30e0\u306e\u69cb\u7bc9\u3092\u6a21\u7d22\u3057\u3066\u304a\u308a\u307e\u3059\u3002<\/p>\n<\/section>\n<section>\n<h4>\u6240\u5c5e\u30e1\u30f3\u30d0\u30fc<\/h4>\n<p><span class=\"bold\">\u4e0d\u6574\u8108\u8a3a\u7642\u306b\u5f93\u4e8b\uff1a<\/span><br \/>\n\u91d1\u53e4\u5584\u660e\u5ba2\u54e1\u6559\u6388\u3001\u7530\u6751\u5cfb\u592a\u90ce\u52a9\u6559\u3001\u9577\u8c37\u5ddd\u5bdb\u52a9\u6559<\/p>\n<p><span class=\"bold\">\u30c8\u30e9\u30f3\u30b9\u30ec\u30fc\u30b7\u30e7\u30ca\u30eb\u30ea\u30b5\u30fc\u30c1\uff08\u907a\u4f1d\u5b50\u89e3\u6790\u3001\u6a5f\u80fd\u89e3\u6790\uff09\u306b\u5f93\u4e8b\uff1a<\/span><br \/>\n\u4e2d\u5cf6\u5fe0\u5ba2\u54e1\u51c6\u6559\u6388\u3001\u677e\u4e95\u7f8e\u7d00\u3055\u3093\uff08\u7814\u7a76\u54e1\uff09<\/p>\n<\/section>\n<section>\n<h4>\u907a\u4f1d\u5b50\u89e3\u6790\u306b\u95a2\u3059\u308b\u304a\u554f\u3044\u5408\u308f\u305b\u7a93\u53e3<\/h4>\n<p>\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u306e\u907a\u4f1d\u5b50\u89e3\u6790\u3092\u3054\u5e0c\u671b\u306e\u65b9\u306f\u3001\u4e0b\u8a18\u3078\u3054\u4e00\u5831\u4e0b\u3055\u3044\u3002<br \/>\n\u7fa4\u99ac\u5927\u5b66\u533b\u5b66\u90e8\u9644\u5c5e\u75c5\u9662\u3000\u5faa\u74b0\u5668\u5185\u79d1<br \/>\n\u4e2d\u5cf6\u5fe0<br \/>\ne-mail: tnakajim@gunma-u.ac.jp<\/p>\n<\/section>\n<section>\n<h4>\u7814\u7a76\u30d7\u30ed\u30b8\u30a7\u30af\u30c8\u306e\u7d39\u4ecb<\/h4>\n<p>\u6b21\u4e16\u4ee3\u30b7\u30fc\u30af\u30a8\u30f3\u30b9\u306e\u5c0e\u5165\u306b\u3088\u308a\u3001\u907a\u4f1d\u6027QT\u5ef6\u9577\u75c7\u5019\u7fa4(LQTS)\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3001\u30ab\u30c6\u30b3\u30e9\u30df\u30f3\u8a98\u767a\u6027\u591a\u5f62\u6027\u5fc3\u5ba4\u983b\u62cd\u306a\u3069\u306e\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u3068\u95a2\u9023\u3059\u308b\u591a\u304f\u306e\u907a\u4f1d\u5b50\u5909\u7570\u304c\u540c\u5b9a\u3055\u308c\u3001\u307e\u305f\u3001\u75be\u60a3\u306e\u75c5\u614b\u3082\u89e3\u660e\u3055\u308c\u3064\u3064\u3042\u308a\u3001\u3055\u3089\u306b\u3001\u6700\u9069\u306a\u6cbb\u7642\u6cd5\u3082\u78ba\u7acb\u3057\u3064\u3064\u3042\u308a\u307e\u3059\u3002\u7279\u306bLQTS\u3067\u306f\u907a\u4f1d\u5b50\u578b\u306b\u3088\u308a\u6700\u9069\u306a\u6cbb\u7642\u6cd5\u306f\u7570\u306a\u308b\u3053\u3068\u304c\u660e\u3089\u304b\u306b\u306a\u3063\u3066\u304a\u308a\u307e\u3059\u3002\u4e00\u65b9\u3001\u7279\u7570\u53ca\u3073\u591a\u5f69\u306a\u8868\u73fe\u578b\u3092\u5448\u3059\u308b\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u75c7\u4f8b\u30fb\u5bb6\u7cfb\u3082\u5c11\u306a\u304b\u3089\u305a\u5b58\u5728\u3057\u307e\u3059\u304c\u3001\u75be\u60a3\u3068\u95a2\u9023\u3059\u308b\u907a\u4f1d\u5b50\u5909\u7570\u3084\u75c5\u614b\u306f\u672a\u89e3\u660e\u306e\u3053\u3068\u304c\u591a\u304f\u3001\u6cbb\u7642\u6cd5\u3082\u78ba\u7acb\u3057\u3066\u3044\u306a\u3044\u306e\u304c\u73fe\u72b6\u3067\u3059\u3002<br \/>\n\u6211\u3005\u306f\u3001\u3053\u308c\u307e\u3067\u306b\u7279\u7570\u53ca\u3073\u591a\u5f69\u306a\u8868\u73fe\u578b\u3092\u5448\u3059\u308b\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u75c7\u4f8b\u30fb\u5bb6\u7cfb\u3092\u591a\u304f\u7d4c\u9a13\u3057\u3001\u6b21\u4e16\u4ee3\u30b7\u30fc\u30af\u30a8\u30f3\u30b9\uff08\u30d1\u30cd\u30eb\u89e3\u6790\u3001\u5168\u30a8\u30af\u30bd\u30f3\u89e3\u6790\uff09\u3092\u99c6\u4f7f\u3057\u3001\u3053\u308c\u3089\u306e\u75c7\u4f8b\u30fb\u5bb6\u7cfb\u306b\u304a\u3044\u3066\u591a\u304f\u306e\u907a\u4f1d\u5b50\u5909\u7570\u3092\u540c\u5b9a\u3057\u5f97\u3066\u304a\u308a\u307e\u3059\u3002\u3055\u3089\u306b\u540c\u5b9a\u3055\u308c\u305f\u907a\u4f1d\u5b50\u5909\u7570\u306e\u6a5f\u80fd\u7570\u5e38\u3092\u89e3\u660e\u3059\u308b\u3053\u3068\u306b\u3088\u308a\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u306e\u5206\u5b50\u75c5\u614b\u3092\u89e3\u660e\u3057\u3001\u5c06\u6765\u306e\u65b0\u898f\u6cbb\u7642\u6cd5\u3092\u958b\u767a\u3001\u78ba\u7acb\u3059\u308b\u305f\u3081\u306e\u77e5\u898b\u3092\u5f97\u308b\u3053\u3068\u3092\u76ee\u7684\u306b\u7814\u7a76\u3092\u884c\u3063\u3066\u304a\u308a\u307e\u3059\u3002<\/p>\n<\/section>\n<section>\n<h4>\u6700\u8fd1\u306e\u4e3b\u306a\u7814\u7a76\u6210\u679c<\/h4>\n<h5>\u7279\u7570\u53ca\u3073\u591a\u5f69\u306a\u8868\u73fe\u578b\u3092\u5448\u3057\u305f\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3067\u540c\u5b9a\u3055\u308c\u305fSCN5A\u5909\u7570\u306e\u6a5f\u80fd\u7570\u5e38\u306e\u89e3\u660e\uff1a fast inactivation \u53ca\u3073closed-state inactivation\u306e\u691c\u8a0e<\/h5>\n<p>\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u306e\u5fc3\u30a4\u30d9\u30f3\u30c8\u306e\u767a\u75c7\u306f\u5b89\u9759\u6642\u3084\u7761\u7720\u6642\u306b\u591a\u3044\u3053\u3068\u304c\u77e5\u3089\u308c\u3066\u304a\u308a\u307e\u3059\u3002\u3057\u304b\u3057\u306a\u304c\u3089\u3001\u6211\u3005\u306f\u3001\u6d1e\u6a5f\u80fd\u4e0d\u5168\u3001\u4e0a\u5ba4\u6027\u983b\u8108\u6027\u4e0d\u6574\u8108\u3092\u5408\u4f75\u3057\u3001\u904b\u52d5\u4e2d\u306b\u5fc3\u30a4\u30d9\u30f3\u30c8\u3092\u7e70\u308a\u8fd4\u3057\u767a\u75c7\u3057\u305f\u89aa\u5b50\u4f8b\u3092\u898b\u51fa\u3057\uff08\u4e9c\u578b\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\uff09\u3001\u65b0\u898fSCN5A R1632C\u5909\u7570\uff08domain \u2163-segment 4: D\u2163-S4\u306e\u5909\u7570\uff09\u3092\u540c\u5b9a\u3057\u5f97\u307e\u3057\u305f(\u56f31)\u3002(Nakajima et al, Heart Rhythm 2015) \u30d1\u30c3\u30c1\u30af\u30e9\u30f3\u30d7\u6cd5\u306b\u3088\u308b\u6a5f\u80fd\u89e3\u6790\u3067\u306f\u3001R1632C\u5909\u7570\u306f\u30ca\u30c8\u30ea\u30a6\u30e0\u96fb\u6d41(INa)\u306efast inactivation\u304b\u3089\u306e\u56de\u5fa9\u304c\u8457\u660e\u306b\u9045\u5ef6\u3057\u3001fast inactivation\u306e\u5b89\u5b9a\u6027\u304c\u5897\u5f37\u3057\u3066\u3044\u307e\u3057\u305f\u3002\u305d\u306e\u305f\u3081\u3001\u9ad8\u983b\u5ea6\u523a\u6fc0\u306b\u3088\u308aR1632C-INa\u306f\u8457\u660e\u306a\u6e1b\u8870\u3092\u8a8d\u3081\u307e\u3057\u305f\u3002\u3053\u308c\u3089\u306e\u3053\u3068\u304b\u3089\u3001\u672c\u75c7\u4f8b\u3067\u306f\u904b\u52d5\u306b\u3088\u308b\u5fc3\u62cd\u6570\u4e0a\u6607\u306b\u3068\u3082\u306a\u3044INa\u304c\u3055\u3089\u306b\u6e1b\u5c11\u3057\u5fc3\u30a4\u30d9\u30f3\u30c8\u3092\u767a\u75c7\u3057\u305f\u3068\u8003\u3048\u3089\u308c\u307e\u3057\u305f\u3002\u901a\u5e38\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3067\u306f\u3001\u03b2\u523a\u6fc0\u85ac\u304c\u6297\u4e0d\u6574\u8108\u4f5c\u7528\u3092\u767a\u63ee\u3057\u3001\u03b2\u906e\u65ad\u85ac\u306f\u907f\u3051\u308b\u3079\u304d\u85ac\u5264\u3068\u3055\u308c\u3066\u304a\u308a\u307e\u3059\u304c\u3001\u4e9c\u578b\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3067\u306f\u03b2\u523a\u6fc0\u85ac\u306f\u75c5\u614b\u3092\u60aa\u5316\u3055\u305b\u308b\u53ef\u80fd\u6027\u3084\u3001\u9006\u306b\u03b2\u906e\u65ad\u85ac\u306e\u6709\u52b9\u6027\u304c\u793a\u5506\u3055\u308c\u307e\u3057\u305f\u3002<br \/>\n\u3055\u3089\u306b\u3001\u6700\u8fd1\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3001\u6d1e\u4e0d\u5168\u75c7\u5019\u7fa4\u3001\u4e0a\u5ba4\u6027\u983b\u8108\u6027\u4e0d\u6574\u8108\u3092\u5448\u3057\u305f\u4ed6\u306e\u4e00\u75c7\u4f8b\u306b\u65b0\u898fSCN5A N1541D\u5909\u7570\uff08domain \u2163-segment 1: D\u2163-S1\u306e\u5909\u7570\uff09\u3092\u540c\u5b9a\u3057\u5f97\u307e\u3057\u305f(\u56f31)\u3002(Dharmawan et al, J Mol Cell Cardiol 2019) R1632C\u5909\u7570\u30ad\u30e3\u30ea\u30a2\u3068N1541D\u5909\u7570\u30ad\u30e3\u30ea\u30a2\u306f\u985e\u4f3c\u3057\u305f\u8868\u73fe\u578b\u3092\u5448\u3057\u305f\u3053\u3068\u304b\u3089\u3001\u305d\u306e\u6a5f\u80fd\u7570\u5e38\u3092\u30d1\u30c3\u30c1\u30af\u30e9\u30f3\u30d7\u6cd5\u306b\u3066\u89e3\u6790\u3057\u6bd4\u8f03\u3057\u305f\u3068\u3053\u308d\u3001N1541D\u306f\u91ce\u751f\u578b\u3068\u6bd4\u3079\u3001INa\u306esteady-state inactivation curve (SSIC)\u306e\u8457\u660e\u306a\u904e\u5206\u6975\u30b7\u30d5\u30c8\u3092\u8a8d\u3081\u3001\u305d\u308c\u306f\u3001closed-state inactivation\uff1aCSI\u306e\u5897\u5f37\u306b\u8d77\u56e0\u3057\u3066\u3044\u307e\u3057\u305f(\u56f32)\u3002N1541D\u3068\u540c\u69d8\u306bSSIC\u306e\u8457\u660e\u306a\u904e\u5206\u6975\u30b7\u30d5\u30c8\u3092\u304d\u305f\u3057\u305fR1632C\u5909\u7570\uff08D\u2163-S4\u306e\u5909\u7570\uff09\u306b\u304a\u3044\u3066\u3082CSI\u304c\u5897\u5f37\u3057\u3001CSI\u306e\u901f\u5ea6\u306f\u91ce\u751f\u578b\u3068\u6bd4\u3079\u8efd\u5ea6\u4fc3\u9032\u3057\u3066\u3044\u307e\u3057\u305f\u304c(\u56f32)\u3001CSI\u304b\u3089\u306e\u56de\u5fa9\u306e\u901f\u5ea6\u306f\u91ce\u751f\u578b\u3068\u6bd4\u3079\u8457\u660e\u306b\u9045\u5ef6\u3057\u3066\u3044\u307e\u3057\u305f\uff08tau-\u91ce\u751f\u578b: 1.90\u00b10.16 ms, R1632C: 53.0\u00b12.5 ms, P&lt;0.01 vs \u91ce\u751f\u578b\uff09(\u56f33)\u3002\u4e00\u65b9\u3001N1541D\u306eCSI\u306e\u901f\u5ea6\u306f\u91ce\u751f\u578b\u3068\u6bd4\u3079\u8457\u660e\u306b\u4fc3\u9032\u3057\u3066\u3044\u307e\u3057\u305f\u304c\uff08tau-\u91ce\u751f\u578b: 65.8\u00b17.4 ms, N1541D: 13.7\u00b11.1 ms, P&lt;0.01 vs \u91ce\u751f\u578b\uff09\u3001CSI\u304b\u3089\u306e\u56de\u5fa9\u306e\u901f\u5ea6\u306f\u91ce\u751f\u578b\u3068\u307b\u307c\u540c\u7b49\u3067\u3057\u305f(\u56f33)\u3002N1541D\u3001R1632C\u306f\u3068\u3082\u306bCSI\u306e\u5897\u5f37\u306b\u3088\u308a\u8457\u660e\u306aINa\u6e1b\u5f31\u3092\u304d\u305f\u3057\u307e\u3057\u305f\u304c\u3001\u305d\u306e\u30e1\u30ab\u30cb\u30ba\u30e0\u306f\u7570\u306a\u308b\u3053\u3068\u304c\u660e\u3089\u304b\u3068\u306a\u308a\u307e\u3057\u305f\u3002<br \/>\nNav1.4\uff08\u9aa8\u683c\u7b4b\u30bf\u30a4\u30d7\uff09\u3067\u306f\u3001N1366(Nav1.5\u3067\u306fN1541\u306b\u76f8\u5f53)\u3068R1457\uff08Nav1.5\u3067\u306fR1632\u306b\u76f8\u5f53\uff09\u306f\u8fd1\u63a5\u3057\u3066\u304a\u308a\u3001 \u30c1\u30e3\u30cd\u30eb\u6d3b\u6027\u5316-\u4e0d\u6d3b\u6027\u5316\u30d7\u30ed\u30bb\u30b9\u3067\u9023\u7d50\u3057\u3066\u3044\u308b\u3068\u8003\u3048\u3089\u308c\u3066\u3044\u308b\u3053\u3068\u304b\u3089\u3001Nav1.5\u306eN1541\u3068R1632\u3067\u3082\u540c\u69d8\u3068\u8003\u3048\u3089\u308c\u307e\u3059\u3002\u4e21\u5909\u7570\u304c\u7570\u306a\u308b\u30e1\u30ab\u30cb\u30ba\u30e0\u306b\u3088\u308aCSI\u306e\u5897\u5f37\u3092\u304d\u305f\u3057\u305f\u3053\u3068\u306f\u3001Nav1.5\u306e\u69cb\u9020-\u6a5f\u80fd\u9023\u95a2\u306b\u65b0\u305f\u306a\u77e5\u898b\u3092\u3082\u305f\u3089\u3057\u307e\u3057\u305f\u3002\u307e\u305f\u3001CSI\u5897\u5f37\u306b\u3088\u308bINa\u6e1b\u5f31\u306b\u3088\u308a\u591a\u5f69\u306a\u8868\u73fe\u578b\u3092\u5448\u3059\u308b\u3053\u3068\u304c\u8aac\u660e\u53ef\u80fd\u3067\u3042\u308a\u3001\u907a\u4f1d\u5b50\u578b-\u8868\u73fe\u578b\u306e\u89e3\u660e\u306e\u4e00\u52a9\u3068\u306a\u308b\u3068\u8003\u3048\u3089\u308c\u307e\u3057\u305f\u3002<br \/>\n\u3053\u308c\u3089\u306e\u7814\u7a76\u6210\u679c\u306f\u3001\u81e8\u5e8a\u9762\u3067\u306f\u3001\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u306b\u304a\u3051\u308b\u65b0\u898f\u6cbb\u7642\u6307\u91dd\u306e\u57fa\u790e\u3092\u69cb\u7bc9\u3057\u3001\u307e\u305f\u3001\u57fa\u790e\u7814\u7a76\u9762\u3067\u306f\u3001\u30a4\u30aa\u30f3\u30c1\u30e3\u30cd\u30eb\u306e\u69cb\u9020-\u6a5f\u80fd\u9023\u95a2\u306b\u65b0\u305f\u306a\u77e5\u898b\u3092\u3082\u305f\u3089\u3059\u306a\u3069\u3001\u591a\u65b9\u9762\u306b\u6d3e\u751f\u3059\u308b\u53ef\u80fd\u6027\u304c\u3042\u308a\u307e\u3059\u3002<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/gucvmed.med.gunma-u.ac.jp\/0_web\/wp-content\/uploads\/2020\/05\/rinsyo23.png\" alt=\"\" \/><\/p>\n<p>\u5f53\u9662\u3067\u540c\u5b9a\u3057\u305f\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u60a3\u8005\u306eSCN5A\u5909\u7570\u3002<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/gucvmed.med.gunma-u.ac.jp\/0_web\/wp-content\/uploads\/2020\/05\/rinsyo24.png\" alt=\"\" \/><\/p>\n<p>SCN5A\u91ce\u751f\u578b(WT), N1541D\u5909\u7570, R1632C\u5909\u7570\u306eclosed-state inactivation\u306e\u6bd4\u8f03\u3002<br \/>\nA: \u633f\u5165\u30d7\u30ed\u30c8\u30b3\u30fc\u30eb\u3067\u306e\u96fb\u6d41\u8a18\u9332<br \/>\nB: \u8131\u5206\u6975\u30d1\u30eb\u30b9-90 mV\u3067\u306eclosed-state inactivation<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/gucvmed.med.gunma-u.ac.jp\/0_web\/wp-content\/uploads\/2020\/05\/rinsyo25.png\" alt=\"\" \/><\/p>\n<p>SCN5A\u91ce\u751f\u578b(WT), N1541D\u5909\u7570, R1632C\u5909\u7570\u306eclosed-state inactivation\u304b\u3089\u306e\u56de\u5fa9\u306e\u6bd4\u8f03\u3002<br \/>\nA: \u633f\u5165\u30d7\u30ed\u30c8\u30b3\u30fc\u30eb\u3067\u306e\u96fb\u6d41\u8a18\u9332<br \/>\nB: \u904e\u5206\u6975\u30d1\u30eb\u30b9(1-1460ms)\u3067\u306eclosed-state inactivation\u304b\u3089\u306e\u56de\u5fa9<br \/>\nC: \u904e\u5206\u6975\u30d1\u30eb\u30b9(0-12ms)\u3067\u306eclosed-state inactivation\u304b\u3089\u306e\u56de\u5fa9\u3002<\/p>\n<\/section>\n<section>\n<h5>\u30a8\u30d4\u30cd\u30d5\u30ea\u30f3\u8ca0\u8377\u3067\u8457\u660e\u306aQT\u5ef6\u9577\u3092\u304d\u305f\u3057\u305fLQT3\u5bb6\u7cfb\u306e\u540c\u5b9a\u53ca\u3073SCN5A\u5909\u7570\u306e\u6a5f\u80fd\u7570\u5e38\u306e\u89e3\u660e<\/h5>\n<p>\u6211\u3005\u306f\u3001\u30a8\u30d4\u30cd\u30d5\u30ea\u30f3\u8ca0\u8377\u3067\u8457\u660e\u306aQT\u5ef6\u9577\u3092\u304d\u305f\u3057\u305fLQTS\u5bb6\u7cfb\uff08\u767a\u7aef\u8005\u306f\u5fc3\u80ba\u505c\u6b62\u8607\u751f\u5f8c\uff09\u306bSCN5A V1667I\u5909\u7570\u3092\u540c\u5b9a\u3057\u307e\u3057\u305f\u3002(Nakajima et al, J Cardiovasc Electrophysiol in press) \u901a\u5e38\u3001SCN5A\u5909\u7570\u306b\u3088\u308bLQTS (LQT3)\u306f\u3001\u904b\u52d5\u3084\u30a8\u30d4\u30cd\u30d5\u30ea\u30f3\u8ca0\u8377\u3067\u306f\u8457\u660e\u306aQT\u5ef6\u9577\u306f\u304d\u305f\u3055\u306a\u3044\u3053\u3068\u304b\u3089\u3001\u672c\u5bb6\u7cfb\u306f\u907a\u4f1d\u5b50\u578b-\u8868\u73fe\u578b\u306e\u89b3\u70b9\u304b\u3089\u7279\u7570\u3067\u3042\u308b\u3068\u8003\u3048\u3089\u308c\u307e\u3059\u3002\u307e\u305f\u3001LQT3\u3067\u306f\u03b2\u906e\u65ad\u85ac\u306e\u6709\u52b9\u6027\u306fcontroversial\u3067\u3059\u304c\u3001\u672c\u5909\u7570\u306e\u30ad\u30e3\u30ea\u30a2\u3067\u306f\u6709\u52b9\u3067\u3042\u308b\u3053\u3068\u304c\u793a\u5506\u3055\u308c\u307e\u3059\u3002\u91ce\u751f\u578bSCN5A\u3001V1667I SCN5A\u3092tsA201\u7d30\u80de\u306b\u767a\u73fe\u3055\u305b\u3001\u30d1\u30c3\u30c1\u30af\u30e9\u30f3\u30d7\u6cd5\u306b\u3066\u6a5f\u80fd\u89e3\u6790\u3092\u884c\u3063\u305f\u7d50\u679c\u3001V1667I\u306f\u30ca\u30c8\u30ea\u30a6\u30e0\u96fb\u6d41(INa)\u5bc6\u5ea6\u306e\u5897\u52a0\u3001\u4e0d\u6d3b\u6027\u5316\u66f2\u7dda\u306e\u8131\u5206\u6975\u30b7\u30d5\u30c8\u306b\u3088\u308bwindow currents\u306e\u5897\u52a0\u3092\u8a8d\u3081\u307e\u3057\u305f\u3002\u3055\u3089\u306b\u3001protein kinase A activator\u3067\u3042\u308b8-CPT-cAMP\u3092\u6295\u4e0e\u3057\u305f\u3068\u3053\u308d\u3001V1667I\u306f\u91ce\u751f\u578b\u306b\u6bd4\u3057\u3001window currents\u306e\u5897\u52a0\u3092\u8a8d\u3081\u307e\u3057\u305f\u3002SCN5A V1667I\u5909\u7570\u30ad\u30e3\u30ea\u30a2\u3067\u306f\u30a8\u30d4\u30cd\u30d5\u30ea\u30f3\u8ca0\u8377\u3067QT\u5ef6\u9577\u3092\u304d\u305f\u3059\u5206\u5b50\u30e1\u30ab\u30cb\u30ba\u30e0\u304c\u89e3\u660e\u3055\u308c\u3001\u307e\u305f\u3001\u672c\u5909\u7570\u30ad\u30e3\u30ea\u30a2\u3067\u306f\u03b2\u906e\u65ad\u304c\u6709\u52b9\u3067\u3042\u308b\u3053\u3068\u304c\u793a\u5506\u3055\u308c\u307e\u3057\u305f\u3002<\/p>\n<\/section>\n<section>\n<h5>\u65b0\u898f\u5fc3\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\u306e\u540c\u5b9a<\/h5>\n<p>\u6211\u3005\u306f\u3001\u767a\u4f5c\u6027\u5fc3\u623f\u7d30\u52d5\u3001\u65e9\u671f\u518d\u5206\u6975\/J\u6ce2\uff08\u5fc3\u81d3\u30c1\u30e3\u30cd\u30eb\u75c5\uff09\u3068\u5c0f\u5150\u671f\u306b\u3066\u3093\u304b\u3093\uff08\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\uff09\u3092\u5408\u4f75\u3057\u305f10\u4ee3\u59c9\u59b9\uff08\u59c9\uff1a19\u6b73\u3001\u59b9\uff1a16\u6b73\u6642\u306b\u7a81\u7136\u6b7b\uff09\u3092\u7d4c\u9a13\u3057\u307e\u3057\u305f\u3002\u767a\u7aef\u8005\uff08\u59c9\uff09\u306e\u5168\u30a8\u30af\u30bd\u30f3\u89e3\u6790\u306e\u7d50\u679c\u3001KCND3 V392I\u5909\u7570\u3092\u540c\u5b9a\u3057\u3001\u59b9\u3082\u672c\u5909\u7570\u3092\u6709\u3057\u3066\u3044\u307e\u3057\u305f\u3002\u767a\u7aef\u8005\u306b\u30ad\u30cb\u30b8\u30f3\u3092\u6295\u4e0e\u3057\u305f\u3068\u3053\u308d\u3001\u5fc3\u623f\u7d30\u52d5\u767a\u4f5c\u306e\u983b\u5ea6\u306f\u6e1b\u5c11\u3057\u3001\u307e\u305f\u3001\u5fc3\u96fb\u56f3\u4e0aJ\u6ce2\u306f\u6e1b\u9ad8\u3057\u307e\u3057\u305f\u3002<br \/>\n\u672c\u5909\u7570\u30ad\u30e3\u30ea\u30a2\u306e\u81e8\u5e8a\u50cf\u306e\u5831\u544a\u306f\u4e4f\u3057\u304f\u3001\u539f\u56e0\u4e0d\u660e\u306e\u7a81\u7136\u6b7b\u75c7\u4f8b\u4e00\u4f8b\uff0820\u6b73\u3001\u7537\u6027\uff09\u3068\u3001\u3066\u3093\u304b\u3093\u75c7\u4f8b\u4e00\u4f8b\uff085\u6b73\u3001\u7537\u5150\uff09\u306b\u540c\u5b9a\u3055\u308c\u305f\u3053\u3068\u304c\u5831\u544a\u3055\u308c\u3066\u3044\u308b\u306e\u307f\u3067\u3057\u305f\u3002(Giudicessi et al, Hum Mutat 2012, Wang et al, Sezure 2019) \u4e00\u65b9\u3001Giudicessi\u3089\u306f\u3001\u672c\u5909\u7570\u306e\u6a5f\u80fd\u89e3\u6790\u3092\u884c\u3044\u3001\u4e00\u904e\u6027\u5916\u5411\u304d\u30ab\u30ea\u30a6\u30e0\u96fb\u6d41(Ito\uff09\u5bc6\u5ea6\u306e\u5897\u52a0\u3001\u4e0d\u6d3b\u6027\u5316\u901f\u5ea6\u306e\u9045\u5ef6\u3001\u4e0d\u6d3b\u6027\u5316\u304b\u3089\u306e\u56de\u5fa9\u306e\u9045\u5ef6\u3092\u304d\u305f\u3059\u3053\u3068\u306b\u3088\u308aIto\u6a5f\u80fd\u5897\u5f37\u3001\u6e1b\u5f31\u306e\u4e21\u65b9\u3092\u304d\u305f\u3059\u3053\u3068\u304c\u660e\u3089\u304b\u3068\u306a\u308a\u307e\u3057\u305f\u3002 (Giudicessi et al. Hum Mutat 2012) \u672c\u5909\u7570\u306b\u3088\u308bIto\u306e\u6a5f\u80fd\u5897\u5f37\u306b\u3088\u308a\u5fc3\u81d3\u30c1\u30e3\u30cd\u30eb\u75c5\u3092\u3001(Olsen et al, Cardiovasc Res 2013, Takayama et al, Heart Rhythm 2019) \u6a5f\u80fd\u6e1b\u5f31\u306b\u3088\u308a\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\u3092\u304d\u305f\u3059\u3068\u8003\u3048\u3089\u308c\u3001(Singh et al, Neurobiol Dis 2006, Aronica et al, Neurobiol Dis 2009) \u6211\u3005\u306f\u3001\u672c\u5909\u7570\u306b\u3088\u308b\u5fc3\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\u3092\u65b0\u898f\u5fc3\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\u3068\u3057\u3066\u63d0\u5531\u3057\u307e\u3057\u305f\u3002<br \/>\n\u3066\u3093\u304b\u3093\u60a3\u8005\u306f\u7a81\u7136\u6b7b\u3092\u304d\u305f\u3059\u3053\u3068\u304c\u591a\u3044\u3068\u3055\u308c\u3066\u304a\u308a\u307e\u3059\u304c\u3001\u7a81\u7136\u6b7b\u3057\u305f\u75c7\u4f8b\u306e\u5c11\u306a\u304f\u3068\u3082\u4e00\u90e8\u306f\u5fc3\u8133\u30c1\u30e3\u30cd\u30eb\u75c5\u306b\u3088\u308b\u53ef\u80fd\u6027\u304c\u3042\u308a\u307e\u3059\u3002\u3066\u3093\u304b\u3093\u60a3\u8005\u306b\u304a\u3044\u3066\u306f\u5fc3\u30c1\u30e3\u30cd\u30eb\u75c5\u3092\u5408\u4f75\u3057\u3066\u3044\u308b\u53ef\u80fd\u6027\u304c\u3042\u308b\u3053\u3068\u304b\u3089\u3001\u907a\u4f1d\u5b50\u5909\u7570\u3092\u540c\u5b9a\u3057\u3001\u7a81\u7136\u6b7b\u4e88\u9632\u7b56\u3092\u8b1b\u3058\u308b\u3053\u3068\u306b\u3088\u308a\u7a81\u7136\u6b7b\u3092\u672a\u7136\u306b\u9632\u3050\u3054\u3068\u304c\u91cd\u8981\u3068\u8003\u3048\u3089\u308c\u307e\u3059\u3002<\/p>\n<\/section>\n<section>\n<h4>\u591a\u65bd\u8a2d\u5171\u540c\u7814\u7a76\u3078\u306e\u53c2\u52a0<\/h4>\n<p>AMED\u7814\u7a76\u8ab2\u984c\u300c\u6d1e\u4e0d\u5168\u75c7\u5019\u7fa4\u306e\u81e8\u5e8a\u60c5\u5831\u30fb\u907a\u4f1d\u5b66\u7684\u89e3\u6790\u306b\u57fa\u3065\u304f\u30ea\u30b9\u30af\u5c64\u5225\u5316\u30a2\u30eb\u30b4\u30ea\u30ba\u30e0\u306e\u958b\u767a\u300d\uff08\u7814\u7a76\u958b\u767a\u4ee3\u8868\u8005\uff1a\u56fd\u7acb\u5faa\u74b0\u5668\u75c5\u7814\u7a76\u30bb\u30f3\u30bf\u30fc\u5206\u5b50\u751f\u7269\u5b66\u3000\u5927\u91ce\u8056\u5b50\u5148\u751f\uff09\u306e\u7814\u7a76\u958b\u767a\u5206\u62c5\u8005\uff08\u4e2d\u5cf6\u5fe0\uff09\u3068\u3057\u3066\u53c2\u52a0\u3057\u3066\u304a\u308a\u307e\u3059\u3002<\/p>\n<\/section>\n<section>\n<h4>\u904e\u53bb5\u5e74\u9593\u306e\u8ad6\u6587\u767a\u8868<\/h4>\n<ul class=\"result\">\n<li>1) Nakajima T, Dharmawan T, Kawabata-Iwakawa R, Tamura S, Hasegawa H, Kobari T, Kaneko Y, Nishiyama M, Kurabayashi M. Biophysical defects of an SCN5A V1667I mutation associated with epinephrine-induced marked QT prolongation. J Cardiovasc Electrophysiol. in press.<\/li>\n<li>2) Nakajima T, Kaneko Y, Dharmawan T, Kurabayashi M. Role of the voltage sensor module in Nav domain IV on fast inactivation in sodium channelopathies: The implication of closed-state inactivation. Channels. 2019; 13: 31-343.<\/li>\n<li>3) Dharmawan T, Nakajima T, Iizuka T, Tamura S, Matsui H, Kaneko Y, Kurabayashi M. Enhanced closed-state inactivation of mutant cardiac sodium channels (SCN5A N1541D and R1632C) through different mechanisms. J Mol Cell Cardiol 2019;13:88-95.<\/li>\n<li>4) Dharmawan T, Nakajima T, Ohno S, Iizuka T, Tamura S, Kaneko Y, Horie M, Kurabayashi M. Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia. Ann Noninvasive Electrocardiol. e12623; 2019.<\/li>\n<li>5) Nakajima T, Sugawara T, Kaneko Y, Kurabayashi M. Atrioventricular block-induced torsades de pointes associated with KCNQ1-G269S. Intern Med 2018; 57: 905-906.<\/li>\n<li>6) Yoshida K, Nakajima T, Kaneko Y, Kurabayashi M. Implication of Left Bundle Branch Block-Related Cardiac Memory in the Initiation of Torsades de Pointes. J Cardiovasc Electrophysiol. 27: 757-758, 2016<\/li>\n<li>7) Nakajima T, Kaneko Y, Saito A, Ota M, Iijima T, Kurabayashi M. Enhanced fast-inactivated state stability of cardiac sodium channels by a novel voltage sensor SCN5A mutation, R1632C, as a cause of atypical Brugada syndrome. Heart Rhythm 12: 2296-2304, 2015<\/li>\n<li>8) Nakajima T, Kaneko Y, Kurabayashi M. Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes. Circ J 79: 1185-1192, 2015<\/li>\n<\/ul>\n<\/section>\n","protected":false},"excerpt":{"rendered":"<p>\u90e8\u9580\u306e\u7d39\u4ecb \u5f53\u79d1\u3067\u306f\u3001\u7fa4\u99ac\u5927\u5b66\u4eba\u3092\u5bfe\u8c61\u3068\u3059\u308b\u533b\u5b66\u7cfb\u7814\u7a76\u502b\u7406\u5be9\u67fb\u59d4\u54e1\u4f1a\u306e\u627f\u8a8d\u3092\u5f97\u3066\u3001\u907a\u4f1d\u6027\u5faa\u74b0\u5668\u75be\u60a3\u306e\u4e2d\u3067\u4e3b\u306b\u907a\u4f1d\u6027\u4e0d\u6574\u8108\u75c7\u5019\u7fa4\u30fb\u5fc3\u7b4b\u75c7\uff08\u907a\u4f1d\u6027QT\u5ef6\u9577\u75c7\u5019\u7fa4\u3001\u30d6\u30eb\u30ac\u30c0\u75c7\u5019\u7fa4\u3001\u30ab\u30c6\u30b3\u30e9\u30df\u30f3\u8a98\u767a\u6027\u591a\u5f62\u6027\u5fc3\u5ba4\u983b\u62cd\u3001\u4e0d\u6574\u8108\u6e90\u6027\u53f3 [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":11,"menu_order":20,"comment_status":"closed","ping_status":"closed","template":"tpl_column2.php","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-39","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/pages\/39","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=39"}],"version-history":[{"count":6,"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/pages\/39\/revisions"}],"predecessor-version":[{"id":934,"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/pages\/39\/revisions\/934"}],"up":[{"embeddable":true,"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=\/wp\/v2\/pages\/11"}],"wp:attachment":[{"href":"https:\/\/gucvmed.med.gunma-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=39"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}