title: Effects of myosin heavy chain isoform switching on Ca2+-activated tension development in single adult cardiac myocytes.
abstract: Cardiac myosin heavy chain (MHC) isoforms are known to play a key role in defining the dynamic contractile behavior of the heart during development. It remains unclear, however, whether cardiac MHC isoforms influence other important features of cardiac contractility, including the Ca2+ sensitivity of isometric tension development. To address this question, adult rats were treated chemically to induce the hypothyroid state and cause a transition in the ventricular cardiac MHC isoform expression pattern from predominantly the alpha-MHC isoform to exclusively the beta-MHC isoform. We found a significant desensitization in the Ca2+ sensitivity of tension development in beta-MHC-expressing ventricular myocytes (pCa50=5. 51+/-0.03, where pCa is -log[Ca2+], and pCa50 is pCa at which tension is one-half maximal) compared with that in predominantly alpha-MHC-expressing myocytes (pCa50=5.68+/-0.05). No differences between the 2 groups were observed in the steepness of the tension-pCa relationship or in the maximum isometric force generated. Instantaneous stiffness measurements were made that provide a relative measure of changes in the numbers of myosin crossbridges attached to actin during Ca2+ activation. Results showed that the relative stiffness-pCa relationship was shifted to the right in beta-MHC-expressing myocytes compared with the alpha-MHC-expressing cardiac myocytes (pCa50=5.47+/-0.05 versus 5.76+/-0.05, respectively). We conclude that MHC isoform switching in adult cardiac myocytes alters the Ca2+ sensitivity of stiffness and tension development. These results suggest that the activation properties of the thin filament are in part MHC isoform dependent in cardiac muscle, indicating an additional role for MHC isoforms in defining cardiac contractile function.
authors.affiliation: Department of Physiology, School of Medicine, University of Michigan, Ann Arbor, MI, USA. metzgerj@umich.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Metzger
authors.forename: P A
authors.initials: PA
authors.lastname: Wahr
authors.forename: D E
authors.initials: DE
authors.lastname: Michele
authors.forename: F
authors.initials: F
authors.lastname: Albayya
authors.forename: M V
authors.initials: MV
authors.lastname: Westfall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007037:Hypothyroidism / Q000139:chemically induced / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000502:physiology*; D009218:Myosins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018995:Myosin Heavy Chains; D009218:Myosins; D002118:Calcium