title: Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle.
abstract: The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change inthickfilament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change inthinfilament structure.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Xuemeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampourakis
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Sevrieva
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Irving
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.|British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom.
authors.forename: Yin-Biao
authors.identifier: 0000-0002-4992-8198
authors.initials: YB
authors.lastname: Sun
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats
chemical_list: D002118:Calcium
keywords: Frank-Starling law of the heart; biophysics; cardiac muscle regulation; fluorescence polarization; length-dependent activation; rat; structural biology; thick filament; thin filament