Schulze K, Heineman F W, Schultheiss H P, Balaban R S
Department of Cardiology, Benjamin Franklin Hospital Free University of Berlin, Germany.
Cell Calcium. 1999 May;25(5):361-70. doi: 10.1054/ceca.1999.0039.
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.
腺嘌呤核苷酸转位酶（ANT）是心肌炎和扩张型心肌病中的一种自身抗原。载体特异性抗体损害心肌能量代谢和心脏功能。它们与肌膜钙通道发生交叉反应，并改变分离心肌细胞中的钙通量。为了测试抗ANT抗体是否能改变完整心脏中的钙稳态，用载体蛋白对豚鼠进行免疫，并在其分离的心脏中加载细胞内钙指示剂INDO-1。通过在364nm处激发，测量410nm和510nm（钙结合指示剂和游离钙指示剂的发射波长）处荧光信号的舒张期和收缩期比率，即“d-s410/510”。这个与收缩周期相关的瞬时钙浓度指标与未免疫对照组的心脏外部功（EHW）相关。免疫动物的EHW较低（对照组为153±47mJ/g/min，免疫组为76±62mJ/g/min，p<0.005），d-s410/510的幅度升高（占整个心动周期平均比率的27.6±4.1%，对照组为21.7±1.2%，p<0.005），且基本上与EHW无关。异丙肾上腺素刺激使所有心脏的EHW增加，但仅使对照心脏的d-s410/510升高。因此，在用ANT免疫的豚鼠心脏中记录到了细胞溶质钙瞬变与功之间的紊乱。它可能促成心肌炎后心力衰竭的免疫病理机制。
