Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium
Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. We compared the molecular mechanism of action of OM on the interaction of atrial and ventricular myosin wit...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2020-08, Vol.528 (4), p.658-663 |
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| creator | Shchepkin, Daniil V. Nabiev, Salavat R. Nikitina, Larisa V. Kochurova, Anastasia M. Berg, Valentina Y. Bershitsky, Sergey Y. Kopylova, Galina V. |
| description | Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. We compared the molecular mechanism of action of OM on the interaction of atrial and ventricular myosin with actin using an optical trap and an in vitro motility assay. In concentrations up to 0.5 μM, OM did not affect the step size of a myosin molecule but reduced it at a higher OM level. OM substantially prolonged the interaction of both isoforms of myosin with actin. However, the interaction characteristics of ventricular myosin with actin were more sensitive to OM than those of atrial myosin. Our results, obtained at the level of isolated proteins, can explain why the impact of OM in therapeutic concentrations on the contractile function of the atrium is less significant as compared to those of the ventricle.
•OM reduces the step size of atrial and ventricular myosin.•OM increases substantially the interaction of cardiac isomyosins with actin.•Ventricular myosin is more sensitive to OM than atrial myosin.•This explains why the OM impact on atrial function is less than on ventricular one. |
| doi_str_mv | 10.1016/j.bbrc.2020.05.108 |
| format | Article |
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•OM reduces the step size of atrial and ventricular myosin.•OM increases substantially the interaction of cardiac isomyosins with actin.•Ventricular myosin is more sensitive to OM than atrial myosin.•This explains why the OM impact on atrial function is less than on ventricular one.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2020.05.108</identifier><identifier>PMID: 32513536</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actin-myosin interaction ; Actins - metabolism ; Animals ; Atrial and ventricular myosin ; Heart Atria - drug effects ; Heart Atria - metabolism ; Heart Ventricles - drug effects ; Heart Ventricles - metabolism ; In vitro motility assay ; Myocardial Contraction - drug effects ; Myosins - metabolism ; Omecamtiv mecarbil ; Optical trap ; Protein Interaction Maps - drug effects ; Swine ; Urea - analogs & derivatives ; Urea - pharmacology</subject><ispartof>Biochemical and biophysical research communications, 2020-08, Vol.528 (4), p.658-663</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-e778780736da01721de99435c343c457feff9e7bc054fbeac5e114c21129289a3</citedby><cites>FETCH-LOGICAL-c422t-e778780736da01721de99435c343c457feff9e7bc054fbeac5e114c21129289a3</cites><orcidid>0000-0003-2976-2108</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2020.05.108$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32513536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shchepkin, Daniil V.</creatorcontrib><creatorcontrib>Nabiev, Salavat R.</creatorcontrib><creatorcontrib>Nikitina, Larisa V.</creatorcontrib><creatorcontrib>Kochurova, Anastasia M.</creatorcontrib><creatorcontrib>Berg, Valentina Y.</creatorcontrib><creatorcontrib>Bershitsky, Sergey Y.</creatorcontrib><creatorcontrib>Kopylova, Galina V.</creatorcontrib><title>Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. We compared the molecular mechanism of action of OM on the interaction of atrial and ventricular myosin with actin using an optical trap and an in vitro motility assay. In concentrations up to 0.5 μM, OM did not affect the step size of a myosin molecule but reduced it at a higher OM level. OM substantially prolonged the interaction of both isoforms of myosin with actin. However, the interaction characteristics of ventricular myosin with actin were more sensitive to OM than those of atrial myosin. Our results, obtained at the level of isolated proteins, can explain why the impact of OM in therapeutic concentrations on the contractile function of the atrium is less significant as compared to those of the ventricle.
•OM reduces the step size of atrial and ventricular myosin.•OM increases substantially the interaction of cardiac isomyosins with actin.•Ventricular myosin is more sensitive to OM than atrial myosin.•This explains why the OM impact on atrial function is less than on ventricular one.</description><subject>Actin-myosin interaction</subject><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Atrial and ventricular myosin</subject><subject>Heart Atria - drug effects</subject><subject>Heart Atria - metabolism</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - metabolism</subject><subject>In vitro motility assay</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myosins - metabolism</subject><subject>Omecamtiv mecarbil</subject><subject>Optical trap</subject><subject>Protein Interaction Maps - drug effects</subject><subject>Swine</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kDtLBDEUhYMouq7-AQtJaTPrvZk32Ij4AsVGwUZCJnMHs0wmmswu7L83w6qFhdV9cM4H5zB2grBAwOJ8uWgarxcCBCwgj79qh80QakgEQrbLZgBQJKLG1wN2GMISADEr6n12kIoc0zwtZuztceOCGXjnneXjO_E1DaM3uiduArfOEw80BDOaNfHRcWdJKxsvPi2-MX10qYHbPxgVISt7xPY61Qc6_p5z9nJz_Xx1lzw83d5fXT4kOhNiTKgsq7KCMi1aBVgKbKmuszTXaZbqLC876rqaykZDnnUNKZ1TTKIFoqhFVat0zs623A_vPlcURmlN0NT3aiC3ClJkiAgFFhilYivV3oXgqZMf3ljlNxJBTrXKpZxqlVOtEvL4q6Lp9Ju_aiy1v5afHqPgYiugmHJtyMugDQ2aWuNJj7J15j_-F4FMiUI</recordid><startdate>20200806</startdate><enddate>20200806</enddate><creator>Shchepkin, Daniil V.</creator><creator>Nabiev, Salavat R.</creator><creator>Nikitina, Larisa V.</creator><creator>Kochurova, Anastasia M.</creator><creator>Berg, Valentina Y.</creator><creator>Bershitsky, Sergey Y.</creator><creator>Kopylova, Galina V.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2976-2108</orcidid></search><sort><creationdate>20200806</creationdate><title>Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium</title><author>Shchepkin, Daniil V. ; Nabiev, Salavat R. ; Nikitina, Larisa V. ; Kochurova, Anastasia M. ; Berg, Valentina Y. ; Bershitsky, Sergey Y. ; Kopylova, Galina V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-e778780736da01721de99435c343c457feff9e7bc054fbeac5e114c21129289a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Actin-myosin interaction</topic><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Atrial and ventricular myosin</topic><topic>Heart Atria - drug effects</topic><topic>Heart Atria - metabolism</topic><topic>Heart Ventricles - drug effects</topic><topic>Heart Ventricles - metabolism</topic><topic>In vitro motility assay</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myosins - metabolism</topic><topic>Omecamtiv mecarbil</topic><topic>Optical trap</topic><topic>Protein Interaction Maps - drug effects</topic><topic>Swine</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shchepkin, Daniil V.</creatorcontrib><creatorcontrib>Nabiev, Salavat R.</creatorcontrib><creatorcontrib>Nikitina, Larisa V.</creatorcontrib><creatorcontrib>Kochurova, Anastasia M.</creatorcontrib><creatorcontrib>Berg, Valentina Y.</creatorcontrib><creatorcontrib>Bershitsky, Sergey Y.</creatorcontrib><creatorcontrib>Kopylova, Galina V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shchepkin, Daniil V.</au><au>Nabiev, Salavat R.</au><au>Nikitina, Larisa V.</au><au>Kochurova, Anastasia M.</au><au>Berg, Valentina Y.</au><au>Bershitsky, Sergey Y.</au><au>Kopylova, Galina V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2020-08-06</date><risdate>2020</risdate><volume>528</volume><issue>4</issue><spage>658</spage><epage>663</epage><pages>658-663</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. We compared the molecular mechanism of action of OM on the interaction of atrial and ventricular myosin with actin using an optical trap and an in vitro motility assay. In concentrations up to 0.5 μM, OM did not affect the step size of a myosin molecule but reduced it at a higher OM level. OM substantially prolonged the interaction of both isoforms of myosin with actin. However, the interaction characteristics of ventricular myosin with actin were more sensitive to OM than those of atrial myosin. Our results, obtained at the level of isolated proteins, can explain why the impact of OM in therapeutic concentrations on the contractile function of the atrium is less significant as compared to those of the ventricle.
•OM reduces the step size of atrial and ventricular myosin.•OM increases substantially the interaction of cardiac isomyosins with actin.•Ventricular myosin is more sensitive to OM than atrial myosin.•This explains why the OM impact on atrial function is less than on ventricular one.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32513536</pmid><doi>10.1016/j.bbrc.2020.05.108</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-2976-2108</orcidid></addata></record> |
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| subjects | Actin-myosin interaction Actins - metabolism Animals Atrial and ventricular myosin Heart Atria - drug effects Heart Atria - metabolism Heart Ventricles - drug effects Heart Ventricles - metabolism In vitro motility assay Myocardial Contraction - drug effects Myosins - metabolism Omecamtiv mecarbil Optical trap Protein Interaction Maps - drug effects Swine Urea - analogs & derivatives Urea - pharmacology |
| title | Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium |
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