High ionic strength depresses muscle contractility by decreasing both force per cross-bridge and the number of strongly attached cross-bridges

dc.contributor.authorWang, Li
dc.contributor.authorBahadır, Anzel
dc.contributor.authorKawai, Masataka
dc.date.accessioned2020-05-01T12:10:20Z
dc.date.available2020-05-01T12:10:20Z
dc.date.issued2015
dc.departmentDÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.descriptionKawai, Masataka/0000-0002-3219-3527en_US
dc.descriptionWOS: 000356379900002en_US
dc.descriptionPubMed: 25836331en_US
dc.description.abstractAn increase in ionic strength (IS) lowers Ca2+ activated tension in muscle fibres, however, its molecular mechanism is not well understood. In this study, we used single rabbit psoas fibres to perform sinusoidal analyses. During Ca2+ activation, the effects of ligands (ATP, Pi, and ADP) at IS ranging 150-300 mM were studied on three rate constants to characterize elementary steps of the cross-bridge cycle. The IS effects were studied because a change in IS modifies the inter- and intra-molecular interactions, hence they may shed light on the molecular mechanisms of force generation. Both the ATP binding affinity (K (1)) and the ADP binding affinity (K (0)) increased to 2-3x, and the Pi binding affinity (K (5)) decreased to 1/2, when IS was raised from 150 to 300 mM. The effect on ATP/ADP can be explained by stereospecific and hydrophobic interaction, and the effect on Pi can be explained by the electrostatic interaction with myosin. The increase in IS increased cross-bridge detachment steps (k (2) and k (-4)), indicating that electrostatic repulsion promotes these steps. However, IS did not affect attachment steps (k (-2) and k (4)). Consequently, the equilibrium constant of the detachment step (K (2)) increased by similar to 100 %, and the force generation step (K (4)) decreased by similar to 30 %. These effects together diminished the number of force-generating cross-bridges by 11 %. Force/cross-bridge (T (56)) decreased by 26 %, which correlates well with a decrease in the Debye length that limits the ionic atmosphere where ionic interactions take place. We conclude that the major effect of IS is a decrease in force/cross-bridge, but a decrease in the number of force generating cross-bridge also takes place. The stiffness during rigor induction did not change with IS, demonstrating that in-series compliance is not much affected by IS.en_US
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HL070041]; The American Heart AssociationAmerican Heart Association [13GRNT16810043]; Higher Educational Council of TurkeyMinistry of National Education - Turkey [82444403-299-1926]en_US
dc.description.sponsorshipThis work was supported by grants from the National Institutes of Health HL070041 (MK), and The American Heart Association 13GRNT16810043 (MK). This study was carried out during Dr. Anzel Bahadir's visit to The University of Iowa with a scholarship (82444403-299-1926) funded by Higher Educational Council of Turkey. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the funding organizations.en_US
dc.identifier.doi10.1007/s10974-015-9412-6en_US
dc.identifier.endpage241en_US
dc.identifier.issn0142-4319
dc.identifier.issn1573-2657
dc.identifier.issue3en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage227en_US
dc.identifier.urihttps://doi.org/10.1007/s10974-015-9412-6
dc.identifier.urihttps://hdl.handle.net/20.500.12684/6152
dc.identifier.volume36en_US
dc.identifier.wosWOS:000356379900002en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal Of Muscle Research And Cell Motilityen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectKineticsen_US
dc.subjectElementary stepsen_US
dc.subjectDebye lengthen_US
dc.subjectIonic atmosphereen_US
dc.subjectSinusoidal analysisen_US
dc.subjectRabbit psoas fibresen_US
dc.titleHigh ionic strength depresses muscle contractility by decreasing both force per cross-bridge and the number of strongly attached cross-bridgesen_US
dc.typeArticleen_US

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