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: Mathew J Jenkins, James T Pearson, Daryl O Schwenke, Amanda J Edgley, Takashi Sonobe, Yutaka Fujii, Hatsue Ishibashi-Ueda, Darren J Kelly, Naoto Yagi, Mikiyasu Shirai
• Journal: Biophysical journal (Biophys J) Vol. 104 Issue 5 Pg. 1065-72 (Mar 05 2013) ISSN: 1542-0086 [Electronic] United States
• PMID: 23473489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Myosins

Topics

• Actin Cytoskeleton (metabolism)
• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Diabetic Cardiomyopathies (metabolism, physiopathology)
• Male
• Myocardial Contraction
• Myosins (metabolism)
• Rats
• Rats, Sprague-Dawley
• Scattering, Small Angle
• Ventricular Pressure
• X-Ray Diffraction