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 microM) 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.
Heyder
S
S
II. Physiologisches Institut, University of Heidelberg, Germany.
Malhotra
A
A
Rüegg
J C
JC
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000235:genetics*; D002316:Cardiotonic Agents / Q000494:pharmacology; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology
D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D002118:Calcium