title: Myosin heads are displaced from actin filaments in the in situ beating rat heart in early diabetes.
abstract: Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I(1,0)/I(1,1)). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy.
authors.affiliation: Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Jenkins
authors.forename: James T
authors.initials: JT
authors.lastname: Pearson
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Schwenke
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Edgley
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Naoto
authors.initials: N
authors.lastname: Yagi
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009218:Myosins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053838:Scattering, Small Angle; D017725:Ventricular Pressure; D014961:X-Ray Diffraction
chemical_list: D009218:Myosins