{"created":"2023-06-19T10:43:11.492782+00:00","id":3360,"links":{},"metadata":{"_buckets":{"deposit":"409719a2-ef00-4f77-bb93-7bc6808c3ae6"},"_deposit":{"created_by":11,"id":"3360","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"3360"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00003360","sets":["30:96:97"]},"author_link":["3686","1988","3687","7488","7489","4127"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-02-28","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"314","bibliographicPageStart":"302","bibliographicVolumeNumber":"52","bibliographic_titles":[{"bibliographic_title":"Cellular physiology and biochemistry : international journal of experimental cellular physiology"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"林, 維光"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"田埜, 郁実"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"小嶋, 亜希子"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"瀬戸, 倫義"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"松浦, 博"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"BACKGROUND/AIMS:\nThe phenylalkylamine class of L-type Ca2+ channel antagonist verapamil prolongs the effective refractory period (ERP) of human atrium, which appears to contribute to the efficacy of verapamil in preventing reentrant-based atrial arrhythmias including atrial fibrillation. This study was designed to investigate the molecular and electrophysiological mechanism underlying the action of verapamil on human Kv1.5 (hKv1.5) channel that determines action potential duration and ERP in human atrium.","subitem_description_type":"Abstract"},{"subitem_description":"METHODS:\nSite-directed mutagenesis created 10 single-point mutations within pore region of hKv1.5 channel. Wholecell patch-clamp method investigated the effect of verapamil on wild-type and mutant hKv1.5 channels heterologously expressed in Chinese hamster ovary cells. Docking simulation was conducted using open-state homology model of hKv1.5 channel pore.","subitem_description_type":"Abstract"},{"subitem_description":"RESULTS:\nVerapamil preferentially blocked hKv1.5 channel in its open state with IC50 of 2.4±0.6 μM (n = 6). The blocking effect of verapamil was significantly attenuated in T479A, T480A, I502A, V505A, I508A, L510A, V512A and V516A mutants, compared with wild-type hKv1.5 channel. Computer docking simulation predicted that verapamil is positioned within central cavity of channel pore and has contact with Thr479, Thr480, Val505, Ile508, Ala509, Val512, Pro513 and Val516.","subitem_description_type":"Abstract"},{"subitem_description":"CONCLUSION:\nVerapamil acts as an open-channel blocker of hKv1.5 channel, presumably due to direct binding to specific amino acids within pore region of hKv1.5 channel, such as Thr479, Thr480, Val505, Ile508, Val512 and Val516. This blocking effect of verapamil on hKv1.5 channel appears to contribute at least partly to prolongation of atrial ERP and resultant antiarrhythmic action on atrial fibrillation in humans.","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Cell Physiol Biochem Press GmbH & Co KG"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"30816676","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.33594/000000022","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© Copyright by the Author(s). Published by Cell Physiol Biochem Press."}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1421-9778","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"林, 維光"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Tano, Ayami"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mi, Xinya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"小嶋, 亜希子"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"SETO, Tomoyoshi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"松浦, 博"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-04-08"}],"displaytype":"detail","filename":"000022.pdf","filesize":[{"value":"3.0 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"000022","url":"https://shiga-med.repo.nii.ac.jp/record/3360/files/000022.pdf"},"version_id":"3d38b28a-cbaa-45f4-accc-8aaa5ac39264"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Amino Acid Substitution","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Animals","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Atrial Fibrillation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Binding Sites","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CHO Cells","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cricetulus","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Humans","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Kv1.5 Potassium Channel","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Molecular Docking Simulation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Point Mutation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Potassium Channel Blockers","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Verapamil","subitem_subject_language":"en","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":"Identification of Verapamil Binding Sites Within Human Kv1.5 Channel Using Mutagenesis and Docking Simulation.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Identification of Verapamil Binding Sites Within Human Kv1.5 Channel Using Mutagenesis and Docking Simulation."}]},"item_type_id":"4","owner":"11","path":["97"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-04-08"},"publish_date":"2019-04-08","publish_status":"0","recid":"3360","relation_version_is_last":true,"title":["Identification of Verapamil Binding Sites Within Human Kv1.5 Channel Using Mutagenesis and Docking Simulation."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:25:38.375676+00:00"}