Phosphorylation status of contractile proteins and functional characteristics in myocardium of dilated cardiomyopathy of Syrian hamster (TO-2 strain)

Abstract

To understand the pathophysiology of hereditary cardiomyopathy, we measured the phosphorylation status of contractile proteins, ventricular light chain 2 (VLC2), troponin I (TnI), troponin T (TnT) and myosin-binding protein C (MyBP-C), and the Ca²⁺-dependence of tension and ATPase activity in skinned trabeculae obtained from normal control (F1B) and cardiomyopathic hamsters (TO-2). To change the phosphorylation status of contractile proteins, isolated trabeculae were exposed to Tyrode's solution containing 30 mM BDM for 30 minutes before skinning. In the BDM-untreated preparations, all the contractile protein phosphorylation levels were higher in F1B than in TO-2, while the Ca²⁺ sensitivities of tension and ATPase activity were substantially lower in F1B than in TO-2. The BDM treatment did not alter the contractile protein phosphorylation levels as well as the Ca²⁺ sensitivities of tension and ATPase activity in TO-2 preparations. However, the BDM treatment decreased the contractile protein phosphorylation levels as well as increased the Ca²⁺ sensitivities of tension and ATPase activity in F1B preparations to the levels similar to those in TO-2 preparations. These results suggest that the increase in Ca²⁺ sensitivities of tension and ATPase activity in TO-2 hamster hearts results from the decreased basal level of TnI and TnT phosphorylation, since the dephosphorylation of VLC2 and MyBP-C has been reported to decrease Ca²⁺ sensitivities. [J Physiol Sci. 2006;56 Suppl:S125]