{"_buckets": {"deposit": "9a481b9e-ba23-4296-b943-07ff5b6f4dd0"}, "_deposit": {"id": "3786", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "3786"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00003786", "sets": ["462"]}, "author_link": ["7025", "7026", "7027", "7028", "7029", "7030", "7031", "7032", "7033", "7034"], "item_1628147817048": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_ab4af688f83e57aa", "subitem_version_type": "AM"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2012-06-15", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "1-2", "bibliographicPageEnd": "23", "bibliographicPageStart": "15", "bibliographicVolumeNumber": "685", "bibliographic_titles": [{"bibliographic_title": "EUROPEAN JOURNAL OF PHARMACOLOGY"}]}]}, "item_6_description_20": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Dihydropyridine Ca2+ channel antagonists (DHPs) block Ca(V)1.2 L-type Ca2+ channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (LI-II) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba2+ currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed-and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels\u0027 kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by LI-II at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the subthreshold potential.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "EUROPEAN JOURNAL OF PHARMACOLOGY. 685(1-3):15-23 (2012)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Nakada, Tsutomu", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.OVkhuNkh.html"}, {"subitem_link_text": "Yamada, Mitsuhiko", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.jhSCupca.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000304205600003"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "ELSEVIER SCIENCE BV"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "22554770"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/22554770", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1016/j.ejphar.2012.04.029"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.ejphar.2012.04.029", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "Copyright© 2012 Elsevier B.V."}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "author"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0014-2999", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0014-2999", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA00639687", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Ca(V)1.2 L-type Ca2+ channel; Voltage-dependent inactivation; Dihydropyridine; Nifedipine; Timothy syndrome; Allosteric model"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "PIG VENTRICULAR MYOCYTES; HIGH-AFFINITY BINDING; CALCIUM-CHANNEL; MOLECULAR DETERMINANTS; DEPENDENT INACTIVATION; GATING CURRENT; BLOCK; ANTAGONISTS; NITRENDIPINE; ISRADIPINE"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Dihydropyridine Ca2+ channel antagonists (DHPs) block Ca(V)1.2 L-type Ca2+ channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (LI-II) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba2+ currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed-and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels\u0027 kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by LI-II at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the subthreshold potential. (C) 2012 Elsevier B.V. All rights reserved."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Sheng,  Xiaona", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7025", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nakada,  Tsutomu", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7026", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kobayashi,  Motohiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7027", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kashihara,  Toshihide", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7028", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shibazaki,  Toshihide", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7029", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Horiuchi-Hirose,  Miwa", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7030", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Gomi,  Simmon", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7031", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hirose,  Masamichi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7032", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Aoyama,  Toshifumi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7033", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamada,  Mitsuhiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "7034", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "Two_mechanistically_distinct_effects_dihydropyridine_nifedipine.pdf", "filesize": [{"value": "802.9 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 802900.0, "url": {"label": "Two_mechanistically_distinct_effects_dihydropyridine_nifedipine.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3786/files/Two_mechanistically_distinct_effects_dihydropyridine_nifedipine.pdf"}, "version_id": "a3d66125-7ef4-4fa8-a110-547ffe1a32a6"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Ca(V)1.2 L-type Ca2+ channel", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Voltage-dependent inactivation", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Dihydropyridine", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Nifedipine", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Timothy syndrome", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Allosteric model", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Two mechanistically distinct effects of dihydropyridine nifedipine on Ca(V)1.2 L-type Ca2+ channels revealed by Timothy syndrome mutation", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Two mechanistically distinct effects of dihydropyridine nifedipine on Ca(V)1.2 L-type Ca2+ channels revealed by Timothy syndrome mutation", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/16908", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2013-04-01"}, "publish_date": "2013-04-01", "publish_status": "0", "recid": "3786", "relation": {}, "relation_version_is_last": true, "title": ["Two mechanistically distinct effects of dihydropyridine nifedipine on Ca(V)1.2 L-type Ca2+ channels revealed by Timothy syndrome mutation"], "weko_shared_id": -1}