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

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) as well as 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 TO-2 (pCa₅₀ 5.64 ± 0.04 in tension and 5.65 ± 0.04 in ATPase activity) than in F1B (pCa₅₀ 5.48 ± 0.03 in tension and 5.51 ± 0.03 in ATPase activity). No significant difference in their maximum values was 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 Ca²⁺ sensitivities of tension development and ATPase activity in TO-2 hearts results 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.