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

TY - JOUR

T1 - Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle

AU - Zhang, Xuemeng

AU - Kampourakis, Thomas

AU - Yan, Ziqian

AU - Sevrieva, Ivanka

AU - Irving, Malcolm

AU - Sun, Yin-biao

PY - 2017/2/23

Y1 - 2017/2/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016294873&partnerID=8YFLogxK

U2 - 10.7554/eLife.24081

DO - 10.7554/eLife.24081

M3 - Article

AN - SCOPUS:85016294873

SN - 2050-084X

VL - 6

SP - 1

EP - 16

JO - eLife

JF - eLife

M1 - e24081

ER -