Myofibrillar Ca2+ sensitivity of cardiomyopathic hamster hearts

We studied the Ca²⁺ responsiveness of skinned muscle fibre preparations from the right and left ventricles of normal (FIB) and genetically cardiomyopathic (Bio-To-2) Syrian hamsters. Thus, we compared the Ca²⁺/force relationships of preparations from myopathic hamsters to those of age-matched (11–16 months old) normal animals. The pCa (i.e. –log₁₀[Ca²⁺]) required for 50% force activation (Ca²⁺ sensitivity) was higher in the myopathic hamsters than in controls (pCa₅₀ values of 5.3±0.03 and 5.17±0.04, respectively); this difference might be due to an alteration in regulatory proteins. Indeed, after extraction (with vanadate) and replacement of troponin I with bovine cardiac troponin the pCa₅₀ values were similar (pCa 5.35) to those of bovine ventricular fibres. The Ca²⁺ sensitizer EMD 53998 (10 M) increased Ca²⁺ sensitivity in preparations from normal and cardiomyopathic hamsters equally, by 0.4 pCa units. Incubation of fibre bundles with the catalytic subunit of cyclicadenosine-monophosphate-dependent protein kinase decreased Ca²⁺ sensitivity, thereby normalizing the enhanced Ca²⁺ responsiveness of fibres from cardiomyopathic hamsters. It is not clear, however, whether the pathologically increased Ca²⁺ sensitivity of the hearts of aged myopathic hamsters reflects a maladaptation, or a compensatory mechanism of the failing heart.