Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle

• Main Authors: Xuemeng Zhang, Thomas Kampourakis, Ziqian Yan, Ivanka Sevrieva, Malcolm Irving, Yin-Biao Sun
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-02-01
• Series: eLife
• Subjects: cardiac muscle regulation; fluorescence polarization; length-dependent activation; thin filament; thick filament; Frank-Starling law of the heart
• Online Access: https://elifesciences.org/articles/24081

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.