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

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xuemeng Zhang ◽  
Thomas Kampourakis ◽  
Ziqian Yan ◽  
Ivanka Sevrieva ◽  
Malcolm Irving ◽  
...  
Keyword(s):  
Heart Muscle ◽  
Structural Changes ◽  
Muscle Cells ◽  
Thick Filament ◽  
Calcium Sensitivity ◽  
Cellular Level ◽  
Thin Filaments ◽  
Thick Filaments ◽  
Filament Structure ◽  
Heart Muscle Cells

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.

scholarly journals Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments

2016 ◽  
Vol 113 (21) ◽  
pp. E3039-E3047 ◽  
Author(s):  
Thomas Kampourakis ◽  
Yin-Biao Sun ◽  
Malcolm Irving
Keyword(s):  
Light Chain ◽  
Heart Muscle ◽  
Calcium Binding ◽  
Structural Changes ◽  
Thick Filament ◽  
Calcium Sensitivity ◽  
Active Force ◽  
Thin Filaments ◽  
Filament Axis ◽  
Filament Structure

Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease.

scholarly journals Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells

2014 ◽  
Vol 111 (52) ◽  
pp. 18763-18768 ◽  
Author(s):  
Thomas Kampourakis ◽  
Ziqian Yan ◽  
Mathias Gautel ◽  
Yin-Biao Sun ◽  
Malcolm Irving
Keyword(s):  
Heart Muscle ◽  
Protein C ◽  
Binding Protein ◽  
Muscle Cells ◽  
Thin Filaments ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Thick Filaments ◽  
Heart Muscle Cells ◽  
Myosin Binding

Modulation of Striated Muscle Function is Reflected by Thick Filament Structure.

2000 ◽  
Vol 6 (S2) ◽  
pp. 76-77
Author(s):  
Rhea J.C. Levine ◽  
Irina Kulakovskaya ◽  
H. Lee Sweeney ◽  
Saul Winegrad ◽  
Zhaohui Yang
Keyword(s):  
Structural Changes ◽  
Striated Muscle ◽  
Contractile Function ◽  
Thick Filament ◽  
Calcium Sensitivity ◽  
Thin Filaments ◽  
Calcium Dependent ◽  
Regulation Of Activity ◽  
Myosin Binding ◽  
Tissue Specimens

In mammalian skeletal and cardiac muscles, regulation of activity occurs when calcium binds to troponin on thin filaments, which ultimately results in exposure of myosin-binding sites on actin. However, modulation of contractile function, affecting such parameters as calcium sensitivity, the rate of rise of tension, the expression of maximum tension and/or the rate of onset of relaxation, is also calcium dependent. It is, in part, a property of the thick filament itself and its component myosin and/or accessory proteins. Among these are phosphorylation of myosin regulatory light chains or light chain 2 (RLCs; LC2) and in cardiac, but not skeletal fibers, phosphorylation of myosin-binding protein C (MyBP-C).Gentle methods of separating thick filaments from small tissue specimens, subjected to various experimental protocols designed to explore the functional parameters of such modulatory activities, allow examination of any accompanying structural changes.

Unravelling the ultrastructural details of αT‐catenin‐deficient cell–cell contacts between heart muscle cells by the use of FIB‐SEM

2019 ◽  
Vol 279 (3) ◽  
pp. 189-196 ◽  
Author(s):  
B. VANSLEMBROUCK ◽  
A. KREMER ◽  
F. VAN ROY ◽  
S. LIPPENS ◽  
J. VAN HENGEL
Keyword(s):  
Heart Muscle ◽  
Muscle Cells ◽  
Cell Contacts ◽  
Deficient Cell ◽  
Heart Muscle Cells ◽  
Cell Cell

Effect of pentobarbital on sodium permeability of heart muscle cells

1984 ◽  
Vol 98 (2) ◽  
pp. 1088-1091
Author(s):  
N. V. Dmitrieva ◽  
E. I. Shtresgeim ◽  
N. A. Burnashev ◽  
V. V. Chernokhvostov
Keyword(s):  
Heart Muscle ◽  
Muscle Cells ◽  
Sodium Permeability ◽  
Heart Muscle Cells

Characteristics of active Na transport in intact cardiac cells

1979 ◽  
Vol 236 (2) ◽  
pp. H189-H199 ◽  
Author(s):  
H. G. Glitsch
Keyword(s):  
Heart Muscle ◽  
Muscle Cells ◽  
Cardiac Cells ◽  
Na Transport ◽  
Concentration Gradients ◽  
Experimental Conditions ◽  
Na Pump ◽  
Na Efflux ◽  
Heart Muscle Cells ◽  
K Concentration

An active Na transport maintains the Na and K concentration gradients across the cell membrane of many cells and restores them following excitation. Heart muscle cells display frequent electrical discharges and thus the cardiac Na pump is of fundamental functional significance. Some methods for studying active Na transport are described. The active Na efflux from heart muscle cells is activated by an increase in the intracellular Na and the extracellular K concentration. The linkage between active Na efflux and active K influx varies widely according to the experimental conditions. The cardiac Na pump is electrogenic and can contribute directly to the membrane potential of the cells. The effects of active Na transport on contraction and intercellular coupling in myocardium are discussed.

Sign in / Sign up

Export Citation Format

Share Document