TRPC6 has been previously reported to be involved in cardiac mechanosensitive responses, e.g., the Anrep effect. However, its role in the Frank-Starling mechanism (FSM) remains unclear. This study investigated whether TRPC6 contributes to the stretch-induced increase in contractile force associated with the FSM. Here, we used isolated ventricular cardiomyocytes from wild-type (WT) and TRPC6−/− mice hearts. The cells were electrically stimulated at 4 Hz in normal Tyrode solution at 37 °C. Axial stretches were applied using the carbon fibre technique to generate the end-systolic force-length relation (ESFLR) curve. The slope of the ESFLR curve, an indicator of cellular contractility, was significantly steeper in TRPC6−/− mouse cardiomyocytes than in WT mouse cardiomyocytes. Transcriptome and real-time polymerase chain reaction analysis revealed that the genetic deletion of TRPC6 led to an increase in metallothionein 1 and 2, which is associated with intracellular Zn2+ concentrations ([Zn2+]i), along with an increase in ZIP8, a zinc transporter. Subsequently, zinc imaging unveiled an elevation in [Zn2+]i in TRPC6−/− mouse cardiomyocytes. Interestingly, the addition of Zn2+ to the normal Tyrode solution also prompted the contractility in WT mouse cardiomyocytes, while this augmentation was blocked by rac-3, a ZIP8 inhibitor. These results suggest that TRPC6 contributes to alterations in cardiac muscle contractility, associated with the FSM, by regulating [Zn2+]i via ZIP8.
"},{"@language":"ja","@value":"TRPC6 has been previously reported to be involved in cardiac mechanosensitive responses, e.g., the Anrep effect. However, its role in the Frank-Starling mechanism (FSM) remains unclear. This study investigated whether TRPC6 contributes to the stretch-induced increase in contractile force associated with the FSM. Here, we used isolated ventricular cardiomyocytes from wild-type (WT) and TRPC6−/− mice hearts. The cells were electrically stimulated at 4 Hz in normal Tyrode solution at 37 °C. Axial stretches were applied using the carbon fibre technique to generate the end-systolic force-length relation (ESFLR) curve. The slope of the ESFLR curve, an indicator of cellular contractility, was significantly steeper in TRPC6−/− mouse cardiomyocytes than in WT mouse cardiomyocytes. Transcriptome and real-time polymerase chain reaction analysis revealed that the genetic deletion of TRPC6 led to an increase in metallothionein 1 and 2, which is associated with intracellular Zn2+ concentrations ([Zn2+]i), along with an increase in ZIP8, a zinc transporter. Subsequently, zinc imaging unveiled an elevation in [Zn2+]i in TRPC6−/− mouse cardiomyocytes. Interestingly, the addition of Zn2+ to the normal Tyrode solution also prompted the contractility in WT mouse cardiomyocytes, while this augmentation was blocked by rac-3, a ZIP8 inhibitor. These results suggest that TRPC6 contributes to alterations in cardiac muscle contractility, associated with the FSM, by regulating [Zn2+]i via ZIP8.
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410298742738866944","@type":"Researcher","foaf:name":[{"@language":"ja","@value":"山口 陽平"},{"@language":"en","@value":"Yamaguchi Yohei"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Dept. Pharmacol. Grad. Sch. Med. Sci. Nagoya City Univ."},{"@language":"ja","@value":"名古屋市立大・院医・薬理学"},{"@language":"en","@value":"Dept. Physiol. Asahikawa Med. Univ."},{"@language":"ja","@value":"旭川医科大・医・生理学"}]},{"@id":"https://cir.nii.ac.jp/crid/1410298742738866816","@type":"Researcher","foaf:name":[{"@language":"ja","@value":"金子 智之"},{"@language":"en","@value":"Kaneko Toshiyuki"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Dept. Physiol. Asahikawa Med. Univ."},{"@language":"ja","@value":"旭川医科大・医・生理学"}]},{"@id":"https://cir.nii.ac.jp/crid/1410298742738866817","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Iribe Gentaro"},{"@language":"ja","@value":"入部 玄太郎"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Dept. Physiol. Asahikawa Med. Univ."},{"@language":"ja","@value":"旭川医科大・医・生理学"}]},{"@id":"https://cir.nii.ac.jp/crid/1410298742738866945","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Ohya Susumu"},{"@language":"ja","@value":"大矢 進"}],"jpcoar:affiliationName":[{"@language":"ja","@value":"名古屋市立大・院医・薬理学"},{"@language":"en","@value":"Dept. Pharmacol. Grad. Sch. Med. Sci. Nagoya City Univ."}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"24354953"}],"prism:publicationName":[{"@language":"en","@value":"Proceedings for Annual Meeting of The Japanese Pharmacological Society"},{"@language":"ja","@value":"日本薬理学会年会要旨集"}],"dc:publisher":[{"@language":"en","@value":"Japanese Pharmacological Society"},{"@language":"ja","@value":"公益社団法人 日本薬理学会"}],"prism:publicationDate":"2023","prism:volume":"97","prism:number":"0","prism:startingPage":"2-B-P-006"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","jpcoar:conferenceName":"第97回日本薬理学会年会","jpcoar:conferencePlace":"神戸国際会議場・神戸国際展示場2号館","url":[{"@id":"https://www.jstage.jst.go.jp/article/jpssuppl/97/0/97_2-B-P-006/_pdf"}],"availableAt":"2023","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=cardiac%20myocyte","dc:title":"cardiac myocyte"},{"@id":"https://cir.nii.ac.jp/all?q=ion%20channel","dc:title":"ion channel"},{"@id":"https://cir.nii.ac.jp/all?q=transporter","dc:title":"transporter"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2012331504"},{"@type":"CROSSREF","@value":"10.1254/jpssuppl.97.0_2-b-p-006"},{"@type":"OPENAIRE","@value":"doi_________::e11527cb954295e75406f4e8c6332f18"}]}