Impairment of myocardial calcium homeostasis by antibodies against the adenine nucleotide translocator.
The adenine nucleotide translocator (ANT) is an autoantigen in myocarditis and dilated cardiomyopathy. Carrier-specific antibodies impair myocardial energy metabolism and heart function. They cross-react with a myolemmal calcium channel and alter calcium fluxes in isolated myocytes. To test whether antibodies against the ANT can alter calcium homeostasis in intact hearts, guinea pigs were immunized with the carrier protein and their isolated hearts loaded with the intracellular calcium indicator INDO-1. The diastolic and systolic ratios of fluorescence signals at 410 nm and 510 nm (emission wavelengths of the calcium-bound and calcium-free indicator), 'd-s410/510', were measured by excitation at 364 nm. This index of the transient calcium concentration associated with the contraction cycle correlated with the external heart work (EHW) in non-immunized controls. EHW of immunized animals was lower (76 +/- 62 vs 153 +/- 47 mJ/g/min in controls, p < 0.005) and the amplitude of d-s410/510 was elevated (27.6 +/- 4.1% of the average ratio of the whole heart cycle vs 21.7 +/- 1.2% in controls, p < 0.005) and essentially independent of EHW. Isoproterenol stimulation increased EHW in all hearts but d-s410/510 was hightened in control hearts, only. Thus, a disorder between cytosolic calcium transients and work was recorded in hearts from guinea pigs immunized with the ANT. It may contribute to an immunopathic mechanism of heart failure subsequent to myocarditis.
Schulze
K
K
Department of Cardiology, Benjamin Franklin Hospital Free University of Berlin, Germany.
Heineman
F W
FW
Schultheiss
H P
HP
Balaban
R S
RS
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003971:Diastole / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D006168:Guinea Pigs; D006706:Homeostasis / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000032:analysis; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size; D010101:Oxygen Consumption / Q000502:physiology; D010477:Perfusion; D011863:Radioimmunoassay; D013050:Spectrometry, Fluorescence; D013599:Systole / Q000502:physiology
D000906:Antibodies; D005456:Fluorescent Dyes; D007211:Indoles; D000226:Mitochondrial ADP, ATP Translocases; C048960:indo-1; D002118:Calcium