title: Cardiac troponin T isoforms demonstrate similar effects on mechanical performance in a regulated contractile system.
abstract: Alteration of troponin T (TnT) isoform expression has been reported in human and animal models of myocardial failure. The two adult beef cardiac TnT isoforms (TnT(3) and TnT(4)) were isolated for comparative functional analysis. Thin filaments were reconstituted containing pure populations of the isoforms. The in vitro motility assay was used to directly compare the effect of the two TnT isoforms on force and unloaded shortening as a function of free calcium. We found no significant differences between the two isoforms in terms of calcium sensitivity, cooperativity, or maximal activation (velocity and force) as assessed in a fully calcium-regulated system. Activation by myosin strong binding was similar for thin filaments containing either of the two TnT isoforms. Whereas maximally activated velocity and cooperativity was depressed at pH 6.5, no difference between thin filaments containing the two isoforms was detected. From the small magnitude of the TnT isoform shifts detected in myocardial failure and the lack of significant mechanical effect detected in the motility assay, variable TnT isoform expression is unlikely to be any functional significance in heart failure.
authors.affiliation: Cardiology Unit, Department of Medicine, University of Vermont, Burlington, Vermont 05405, USA. vanburen@physiology.med.uvm.edu
authors.forename: Peter
authors.initials: P
authors.lastname: VanBuren
authors.forename: Shari L
authors.initials: SL
authors.lastname: Alix
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gorga
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Begin
authors.forename: Martin M
authors.initials: MM
authors.lastname: LeWinter
authors.forename: Norman R
authors.initials: NR
authors.lastname: Alpert
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D000199:Actins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D007537:Isometric Contraction; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000737:chemistry; D009218:Myosins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000494:pharmacology*; D011817:Rabbits; D020107:Troponin T / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000199:Actins; D020033:Protein Isoforms; D020107:Troponin T; D009218:Myosins; D002118:Calcium