Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
Xuemeng Zhang,
Thomas Kampourakis,
Ziqian Yan,
Ivanka Sevrieva,
Malcolm Irving,
Yin-Biao Sun
Affiliations
Xuemeng Zhang
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
Thomas Kampourakis
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
Ziqian Yan
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
Ivanka Sevrieva
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
Malcolm Irving
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
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
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 in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.
