title: Effects of pseudo-phosphorylated rat cardiac troponin T are differently modulated by α- and β-myosin heavy chain isoforms.
abstract: Interplay between the protein kinase C (PKC)-mediated phosphorylation of troponin T (TnT)- and myosin heavy chain (MHC)-mediated effects on thin filaments takes on a new significance because: (1) there is significant interaction between the TnT- and MHC-mediated effects on cardiac thin filaments; (2) although the phosphorylation of TnT by PKC isoforms is common to both human and rodent hearts, human hearts predominantly express β-MHC while rodent hearts predominantly express α-MHC. Therefore, we tested how α- and β-MHC isoforms differently affected the functional effects of phosphorylated TnT. Contractile measurements were made on cardiac muscle fibers from normal rats (α-MHC) and propylthiouracil-treated rats (β-MHC), reconstituted with the recombinant phosphomimetic-TnT (T204E; threonine 204 replaced by glutamate). Ca2+ -activated maximal tension decreased differently in α-MHC + T204E (~68%) and β-MHC + T204E (~35%). However, myofilament Ca2+ sensitivity decreased similarly in α-MHC + T204E and β-MHC + T204E, demonstrating that a decrease in Ca2+ sensitivity alone cannot explain the greater attenuation of tension in α-MHC + T204E. Interestingly, dynamic contractile parameters (rates of tension redevelopment, crossbridge (XB) recruitment dynamics, XB distortion dynamics, and XB detachment kinetics) decreased only in α-MHC + T204E. Thus, the transition of thin filaments from the blocked- to closed-state was attenuated in α-MHC + T204E and β-MHC + T204E, but the closed- to open-state transition was attenuated only in α-MHC + T204E. Our study demonstrates that the effects of phosphorylated TnT and MHC isoforms interact to bring about different functional states of cardiac thin filaments.
authors.affiliation: Department of Integrative Physiology and Neuroscience (Formerly VCAPP), Washington State University, 205 Veterinary Biomedical Research Building, Pullman, WA, 99164-7620, USA.
authors.forename: John Jeshurun
authors.initials: JJ
authors.lastname: Michael
authors.forename: Sampath K
authors.initials: SK
authors.lastname: Gollapudi
authors.forename: Murali
authors.initials: M
authors.lastname: Chandra
mesh_terms: D000818:Animals; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000502:physiology*; D010766:Phosphorylation; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000378:metabolism*
chemical_list: C000594638:MYH7 protein, rat; D020033:Protein Isoforms; D020107:Troponin T; D018995:Myosin Heavy Chains