title: Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms.
abstract: 1. Cardiac V3 myosin generates slower actin filament velocities and higher average isometric forces (in an in vitro motility assay) when compared with the V1 isoform. 2. To account for differences in V1 and V3 force and motion generation at the molecular level, we characterized the mechanics and kinetics of single V1 and V3 myosin molecules using a dual laser trap setup. 3. No differences in either unitary displacement (approximately 7 nm) or force (approximately 0.8 pN) were observed between isoforms; however, the duration of unitary displacement events was significantly longer for the V3 isoform at MgATP concentrations > 10 microM. 4. Our results were interpreted on the basis of a cross-bridge model in which displacement event durations were determined by the rates of MgADP release from, and MgATP binding to, myosin. 5. We propose that the release rate of MgADP from V3 myosin is half that of V1 myosin without any difference in their rates of MgATP binding; thus, kinetic differences between the two cardiac myosin isoforms are sufficient to account for their functional diversity.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Palmiter
authors.forename: M J
authors.initials: MJ
authors.lastname: Tyska
authors.forename: D E
authors.initials: DE
authors.lastname: Dupuis
authors.forename: N R
authors.initials: NR
authors.lastname: Alpert
authors.forename: D M
authors.initials: DM
authors.lastname: Warshaw
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007700:Kinetics; D007834:Lasers; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins