title: Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations.
abstract: Cross-bridge kinetics were studied at 20 °C in cardiac muscle strips from transgenic (Tg) mice expressing N-terminal 43 amino acid truncation mutation (Δ43) of myosin essential light chain (ELC), and the results were compared to those from Tg-wild type (WT) mice. Sinusoidal length changes were applied to activated skinned papillary muscle strips to induce tension transients, from which two exponential processes were deduced to characterize the cross-bridge kinetics. Their two rate constants were studied as functions of ATP, phosphate (Pi), ADP, and Ca(2+) concentrations to characterize elementary steps of the cross-bridge cycle consisting of six states. Our results demonstrate for the first time that the cross-bridge kinetics of Δ43 are accelerated owing to an acceleration of the rate constant k 2 of the cross-bridge detachment step, and that the number of strongly attached cross-bridges are decreased because of a reduction of the equilibrium constant K 4 of the force generation step. The isometric tension and stiffness of Δ43 are diminished compared to WT, but the force per cross-bridge is not changed. Stiffness measurement during rigor induction demonstrates a reduction in the stiffness in Δ43, indicating that the N-terminal extension of ELC forms an extra linkage between the myosin cross-bridge and actin. The tension-pCa study demonstrates that there is no Ca(2+) sensitivity change with Δ43, but the cooperativity is diminished. These results demonstrate the importance of the N-terminal extension of ELC in maintaining the myosin motor function during force generation and optimal cardiac performance.
authors: Departments of Anatomy and Cell Biology, and Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
authors: Li
authors: L
authors: Wang
authors: Priya
authors: P
authors: Muthu
authors: Danuta
authors: D
authors: Szczesna-Cordary
authors: Masataka
authors: M
authors: Kawai
mesh_terms: D000244:Adenosine Diphosphate / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D010710:Phosphates / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D018994:Myosin Light Chains; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium
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