Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics

Yihua Wang, Katalin Ajtai, Thomas P. Burghardt

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cardiac ventricular myosin (bmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary bmys translation of actin is the step-size. In vitro and in vivo bmys regulates contractile force and velocity autonomously by remixing three different step-sizes with adaptive stepping frequencies. Cardiac and skeletal actin isoforms have a specific 1: 4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) upregulate skeletal actin in ventriculum probably compensating the diseased muscle's inability to meet demand by adjusting bmys force-velocity characteristics. bmys force-velocity characteristics were compared for skeletal versus cardiac actin substrates using ensemble in vitro motility and single myosin assays. Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing single bmys mechanics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads probably by the unique cardiac essential light chain (ELC) N-terminus/cardiac actin contact at Glu6/Ser358. It modifies bmys force-velocity by stabilizing the ELC N-terminus/cardiac actin association. Uneven onset of the high-force regime for skeletal versus cardiac actin modulates force-velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle.

Original languageEnglish (US)
Article number180143
JournalOpen biology
Volume8
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Actin binding myosin essential light chain
  • Cardiac actin
  • ELC N-terminus/cardiac actin contact
  • Strain-sensitive regulation
  • Ventricular myosin force-velocity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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