Myosin heads are displaced from actin filaments in the in situ beating rat heart in early diabetes

Mathew James Jenkins, James Todd Pearson, Daryl Schwenke, Amanda Jane Edgley, Takashi Sonobe, Yutaka Fujii, Hatsue Ishibashi-Ueda, Darren J Kelly, Naoto Yagi, Mikiyasu Shirai

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10 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1065 - 1072
Number of pages8
JournalBiophysical Journal
Issue number5
Publication statusPublished - 2013

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