Kim C S, Davidoff A J, Maki T M, Doye A A, Gwathmey J K
Whitaker Cardiovascular Research Institute, Boston University School of Medicine, MA 02115, USA.
J Comp Physiol B. 2000 Jun;170(4):295-306. doi: 10.1007/s003600000103.
Global contractile heart failure was induced in turkey poults by furazolidone feeding (700 ppm). Abnormal calcium regulation appears to be a key factor in the pathophysiology of heart failure, but the cellular mechanisms contributing to changes in calcium fluxes have not been clearly defined. Isolated ventricular myocytes from non-failing and failing hearts were therefore used to determine whether the whole heart and ventricular muscle contractile dysfunctions were realized at the single cell level. Whole cell current- and voltage-clamp techniques were used to evaluate action potential configurations and L-type calcium currents, respectively. Intracellular calcium transients were evaluated in isolated myocytes with fura-2 and in isolated left ventricular muscles using aequorin. Action potential durations were prolonged in failing myocytes, which correspond to slowed cytosolic calcium clearing. Calcium current-voltage relationships were normal in failing myocytes; preliminary evidence suggests that depressed transient outward potassium currents contribute to prolonged action potential durations. The number of calcium channels (as measured by radioligand binding) were also similar in non-failing and failing hearts. Isolated ventricular muscles from failing hearts had enhanced inotropic responses, in a dose-dependent fashion, to a calcium channel agonist (Bay K 8644). These data suggest that changes in intracellular calcium mobilization kinetics and longer calcium-myofilament interaction may be able to compensate for contractile failure. We conclude that the relationship between calcium current density and sarcoplasmic reticulum calcium release is a dynamic process that may be altered in the setting of heart failure at higher contraction rates.
通过喂食呋喃唑酮（700 ppm）诱导火鸡雏鸡发生全身性收缩性心力衰竭。钙调节异常似乎是心力衰竭病理生理学中的一个关键因素，但导致钙通量变化的细胞机制尚未明确界定。因此，使用来自非衰竭和衰竭心脏的离体心室肌细胞来确定全心脏和心室肌收缩功能障碍是否在单细胞水平上得以体现。分别使用全细胞电流钳和电压钳技术评估动作电位形态和L型钙电流。使用fura-2评估离体肌细胞中的细胞内钙瞬变，并使用水母发光蛋白评估离体左心室肌中的细胞内钙瞬变。衰竭肌细胞的动作电位时程延长，这与胞质钙清除减慢相对应。衰竭肌细胞中的钙电流-电压关系正常；初步证据表明，瞬时外向钾电流降低导致动作电位时程延长。非衰竭和衰竭心脏中钙通道的数量（通过放射性配体结合测量）也相似。来自衰竭心脏的离体心室肌对钙通道激动剂（Bay K 8644）呈现出剂量依赖性的增强的变力反应。这些数据表明，细胞内钙动员动力学的变化和更长的钙-肌丝相互作用可能能够补偿收缩功能衰竭。我们得出结论，钙电流密度与肌浆网钙释放之间的关系是一个动态过程，在心力衰竭且收缩率较高的情况下可能会发生改变。
