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. -log(10)[Ca2+]) required for 50% force activation (Ca2+ sensitivity) was higher in the myopathic hamsters than in controls (pCa(50) 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 pCa(50) values were similar (pCa 5.35) to those of bovine ventricular fibres. The Ca2+ sensitizer EMD 53998 (10 mu 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 cyclic-adenosine-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.