Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts
Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts
复制标题
DOI：
10.1161/01.res.87.7.588
复制
发表时间：
2000-09-29
影响因子：
20.1
通讯作者：
Lorell, BH
中科院分区：
文献类型：
--
作者：
Ito, K;Yan, X;Lorell, BH
小鼠心肌细胞收缩性和压力超负荷引起的变化尚未完全了解。我们研究了升主动脉瓣狭窄（AS）小鼠在代偿性肥大（4周AS）和早期衰竭后期（7周AS）和对照小鼠的离体左心室肌细胞的收缩储备。用Fluo-3同时测量肌细胞收缩和[Ca 2 +]（i）瞬变。在基线（0.5 Hz，1.5 mmol/L [Ca 2 +]（o），25 ℃），7周AS组的肌细胞缩短幅度和收缩期峰值[Ca 2 +]（i）与对照组无差异，而收缩、舒张和[Ca 2 +]（i）瞬变下降较慢。与对照组相比，7周AS组在高[Ca 2 +]（0）的刺激下，细胞缩短率受到严重抑制，收缩期峰值[Ca 2 +]（i）降低。在快速起搏刺激下，对照组细胞缩短和收缩期峰值[Ca 2 +]（i）增加，但在7周AS中这种反应被抑制。而4周AS对高[Ca~（2+）]（o）刺激和快速起搏的反应与对照组相似。尽管4周和7周AS的Na~+-Ca~（2+）交换蛋白水平均升高，但7周AS的SR Ca~（2+）-ATP酶与受磷蛋白水平的比值较对照组降低，而4周AS则无此变化。这与7周AS肌细胞在高工作状态下增加肌浆网Ca 2+负荷的能力受损有关。在肥大衰竭小鼠肌细胞中，收缩储备降低与收缩期[Ca 2 +]（i）和SR Ca 2+负荷增加受损相关，并模拟人类衰竭肌细胞中的发现。
Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca2+](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca2+](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca2+](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca2+](i) transients were slower. In response to the challenge of high [Ca2+](0), fractional cell shortening was severely depressed with reduced peak-systolic [Ca2+](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca2+](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca2+](o) and rapid pacing in 4-week AS were similar to those of controls, Although protein levels of Na+-Ca2+ exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca2+-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca2+ load during high work states in 7-week AS myocytes, In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca2+](i) and SR Ca2+ load and simulates findings in human failing myocytes.