title: Effects of myosin light chain phosphorylation on length-dependent myosin kinetics in skinned rat myocardium.
abstract: Myosin force production is Ca(2+)-regulated by thin-filament proteins and sarcomere length, which together determine the number of cross-bridge interactions throughout a heartbeat. Ventricular myosin regulatory light chain-2 (RLC) binds to the neck of myosin and modulates contraction via its phosphorylation state. Previous studies reported regional variations in RLC phosphorylation across the left ventricle wall, suggesting that RLC phosphorylation could alter myosin behavior throughout the heart. We found that RLC phosphorylation varied across the left ventricle wall and that RLC phosphorylation was greater in the right vs. left ventricle. We also assessed functional consequences of RLC phosphorylation on Ca(2+)-regulated contractility as sarcomere length varied in skinned rat papillary muscle strips. Increases in RLC phosphorylation and sarcomere length both led to increased Ca(2+)-sensitivity of the force-pCa relationship, and both slowed cross-bridge detachment rate. RLC-phosphorylation slowed cross-bridge rates of MgADP release (∼30%) and MgATP binding (∼50%) at 1.9 μm sarcomere length, whereas RLC phosphorylation only slowed cross-bridge MgATP binding rate (∼55%) at 2.2 μm sarcomere length. These findings suggest that RLC phosphorylation influences cross-bridge kinetics differently as sarcomere length varies and support the idea that RLC phosphorylation could vary throughout the heart to meet different contractile demands between the left and right ventricles.
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164-7620, USA.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Pulcastro
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164-7620, USA.
authors.forename: Peter O
authors.initials: PO
authors.lastname: Awinda
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164-7620, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Breithaupt
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164-7620, USA. Electronic address: btanner@vetmed.wsu.edu.
authors.forename: Bertrand C W
authors.initials: BC
authors.lastname: Tanner
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000737:chemistry*; D004548:Elasticity; D006352:Heart Ventricles / Q000378:metabolism; D007537:Isometric Contraction; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry; D012518:Sarcomeres / Q000378:metabolism*; D013314:Stress, Mechanical; D014783:Viscosity
chemical_list: D018994:Myosin Light Chains; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D009219:Myosin-Light-Chain Kinase; D008274:Magnesium; D002118:Calcium
keywords: Cardiac muscle; Cross-bridge kinetics; Frank-Starling relationship; Length-dependent contraction; Myosin regulatory light chain; Phosphorylation