Phosphorylation status of regulatory proteins and functional characteristics in myocardium of dilated cardiomyopathy of Syrian hamsters.
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 micromol/l/s in ATP consumption) and F1B (42.3 +/- 8.5 mN/mm2 in tension and 0.58 +/- 0.41 micromol/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.
Ohnuki
Yoshiki
Y
Department of Physiology, Tsurumi University School of Dental Medicine, Tsurumi-ku, Yokohama, Japan.
Nishimura
Satoshi
S
Sugiura
Seiryo
S
Saeki
Yasutake
Y
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000378:metabolism; D006224:Cricetinae; D003971:Diastole / Q000502:physiology; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D013599:Systole / Q000502:physiology; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D000099163:Myosin Binding Protein C
D000251:Adenosine Triphosphatases; D002118:Calcium; D024722:Cardiac Myosins; D002352:Carrier Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; D019210:Troponin I; D020107:Troponin T; D000099163:Myosin Binding Protein C; C107184:myosin light chain 2