PHYSIOLSCI : Vol. 58 (2008) , No. 1 15-20

Phosphorylation Status of Regulatory Proteins and Functional Characteristics in Myocardium of Dilated Cardiomyopathy of Syrian Hamsters

Yoshiki Ohnuki¹⁾, Satoshi Nishimura²⁾, Seiryo Sugiura³⁾ and Yasutake Saeki¹⁾

1) Department of Physiology, Tsurumi University School of Dental Medicine
2) Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
3) Biomechanics Laboratory, Institute of Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo

(Received October 31, 2007)
(Accepted January 2, 2008)

Abstract: To understand the pathophysiology of hereditary cardiomyopathy, we measured the phosphorylation status of regulatory proteins, troponin I (TnI), troponin T (TnT), myosin light chain 2 (MLC2), and myosin-binding protein C (MyBP-C), and the Ca²⁺-dependence of tension development and ATPase activity in skinned right ventricular trabeculae obtained from cardiomyopathic (TO-2 strain, n = 8) and control (F1B strain, n = 8) hamsters. The Ca²⁺ sensitivities of tension development and ATPase activity (mean ± SD) were significantly (P < 0.0001) higher in the TO-2 strain (pCa₅₀ 5.64 ± 0.04 in tension and 5.65 ± 0.04 in ATPase activity) than in the F1B strain (pCa₅₀ 5.48 ± 0.03 in tension and 5.51 ± 0.03 in ATPase activity). No significant differences in their maximum values were observed between TO-2 (40.8 ± 7.4 mN/mm² in tension and 0.52 ± 0.15 μmol/l/s in ATP consumption) and F1B (42.3 ± 8.5 mN/mm² in tension and 0.58 ± 0.41 μmol/l/s in ATP consumption) preparations, indicating that the tension cost (ATPase activity/tension development) in TO-2 was quite similar to that in F1B. The phosphorylation levels of MLC2 and TnI were significantly (P < 0.01) lower in TO-2 than in F1B. These results suggest that the increase in the Ca²⁺ sensitivities of tension development and the ATPase activity in TO-2 hearts result from the decreased basal level of TnI phosphorylation, and these features can be considered to produce the incomplete diastolic relaxation and partly improve the systolic function in TO-2 hearts.

Key words: dilated cardiomyopathy, phosphorylation status, tension development, ATPase activity, tension cost