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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)
160 Downloads (Pure)

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 in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.

Original languageEnglish
Article numbere24081
Pages (from-to)1-16
JournaleLife
Volume6
Early online date23 Feb 2017
DOIs
Publication statusPublished - 23 Feb 2017

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