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

• Published in: eLife Vol. 6
• Main Authors: Zhang, Xuemeng, Kampourakis, Thomas, Yan, Ziqian, Sevrieva, Ivanka, Irving, Malcolm, Sun, Yin-Biao
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 23.02.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Actin Cytoskeleton - metabolism; Animals; Biophysics and Structural Biology; Calcium; Calcium - metabolism; Calcium-binding protein; Cardiac muscle; cardiac muscle regulation; Filaments; Fluorescence; fluorescence polarization; Frank-Starling law of the heart; Heart; Heart diseases; Heart rate; length-dependent activation; Myocardial Contraction; Myocytes, Cardiac - physiology; Myosin; Rats; Signal transduction; thick filament; thin filament; Troponin; Troponin C; thin filament; Frank-Starling law of the heart; length-dependent activation; rat; cardiac muscle regulation; fluorescence polarization; structural biology; thick filament; biophysics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.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 filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in filament structure.