Lim C C, Apstein C S, Colucci W S, Liao R
Whitaker Cardiovascular Institute, Boston University School of Medicine, USA.
J Mol Cell Cardiol. 2000 Nov;32(11):2075-82. doi: 10.1006/jmcc.2000.1239.
Increased heart rate enhances cardiac contractility and accelerates relaxation. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be impaired in senescent myocardium. While senescent myocardium is characterized by decreased sarcoplasmic reticulum calcium ATPase activity, it is unclear if altered calcium regulation is directly responsible for the attenuated contractility and relaxation observed with increasing pacing frequency in aged myocardium. We examined this issue using freshly dissociated left ventricular myocytes, isolated from young adult and senescent mouse hearts. Myocytes were paced from 2 to 9 Hz at 37 degrees C, and cell shortening and Ca(2+)were simultaneously measured using video edge-detection and fura-2 fluorescence, respectively. In adult myocytes, increasing the pacing rate resulted in a progressive increase in percent cell shortening (CS) (P<0.01). This positive CS-frequency relationship was paralleled by an increase in Ca(2+)transient amplitude (P<0.05). In contrast, the CS-frequency relationship was blunted in senescent myocytes with no increase in percent CS or Ca(2+)transient amplitude with increasing pacing rate. With increased pacing, the decreases in time constants (tau) of cell relengthening and Ca(2+)transient decay were much steeper in adult compared to senescent myocytes (P<0.05). This study demonstrates that adult mouse myocytes exhibit augmented intracellular Ca(2+)transient amplitude and enhanced intracellular Ca(2+)removal with increasing pacing frequency, resulting in increased cell shortening and enhanced relengthening with frequency. In contrast, senescent mouse myocytes exhibit impaired calcium handling with increasing pacing frequency, which correlated with impairment of both cell shortening and relengthening.
心率增加可增强心肌收缩力并加速舒张。力-频率关系和舒张-频率关系对心肌功能都至关重要，尤其是在应激期间，并且已表明在衰老心肌中这些关系受损。虽然衰老心肌的特征是肌浆网钙ATP酶活性降低，但尚不清楚钙调节改变是否直接导致老年心肌中随着起搏频率增加而观察到的收缩力和舒张减弱。我们使用从年轻成年和衰老小鼠心脏分离的新鲜解离的左心室心肌细胞研究了这个问题。在37℃下将心肌细胞以2至9Hz的频率起搏，并分别使用视频边缘检测和fura-2荧光同时测量细胞缩短和[Ca(2+)]i。在成年心肌细胞中，增加起搏频率导致细胞缩短百分比（CS）逐渐增加（P<0.01）。这种正的CS-频率关系与[Ca(2+)]i瞬变幅度的增加平行（P<0.05）。相比之下，衰老心肌细胞中的CS-频率关系减弱，随着起搏频率增加，CS百分比或[Ca(2+)]i瞬变幅度没有增加。随着起搏增加，成年心肌细胞与衰老心肌细胞相比，细胞再延长和Ca(2+)瞬变衰减的时间常数（tau）下降要陡峭得多（P<0.05）。这项研究表明，成年小鼠心肌细胞随着起搏频率增加表现出细胞内Ca(2+)瞬变幅度增加和细胞内Ca(2+)清除增强，导致细胞缩短增加和频率依赖性再延长增强。相比之下，衰老小鼠心肌细胞随着起搏频率增加表现出钙处理受损，这与细胞缩短和再延长受损相关。
