title: The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.
abstract: Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy.
authors.affiliation: Molecular Physiology Section, Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Davis
authors.forename: S
authors.initials: S
authors.lastname: Hassanzadeh
authors.forename: S
authors.initials: S
authors.lastname: Winitsky
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Satorius
authors.forename: R
authors.initials: R
authors.lastname: Vemuri
authors.forename: A H
authors.initials: AH
authors.lastname: Aletras
authors.forename: H
authors.initials: H
authors.lastname: Wen
authors.forename: N D
authors.initials: ND
authors.lastname: Epstein
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology*; D003001:Cloning, Molecular; D006321:Heart / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011859:Radiography; D024744:Skeletal Muscle Myosins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D024744:Skeletal Muscle Myosins