Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure
Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure
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DOI：
10.1007/s000180050187
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发表时间：
1998-06-01
影响因子：
8
通讯作者：
Undrovinas, AI
中科院分区：
文献类型：
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作者：
Maltsev, VA;Sabbah, HN;Undrovinas, AI
从衰竭的人类心脏和实验诱导的心力衰竭(HF)动物的心脏中分离的心肌细胞中发现了收缩功能的异常。导致这些功能异常的机制(S)尚不完全清楚。在本研究中，我们研究了犬(n=7)左心室(LV)单个心肌细胞动作电位时程、收缩和松弛模式以及相关的细胞内钙瞬变之间的关系。并与正常犬左室肌细胞进行比较。用穿孔膜片钳技术测定心肌细胞动作电位，用FASH 3探针荧光法测定心肌细胞的钙瞬变，用边缘运动检测仪测定心肌细胞的收缩和松弛。HF心肌细胞表现出收缩和松弛的异常模式，其特征是最初的收缩(峰)减弱，然后持续收缩(穹顶)1~8 S，随后延迟松弛。这种模式在低刺激率时更为明显(0.2赫兹时为58%，n=211；0.5赫兹时为21%，n=185)。在0.2赫兹下测量高频心肌细胞的钙瞬变显示出类似的尖峰和穹顶结构。在HF心肌细胞中可以看到的收缩/松弛模式和钙瞬变的穹顶阶段与动作电位的持续平台相一致。应用萨克托毒素(100 NM)或利多卡因(30 MM)缩短动作电位时程，既缩短了收缩/舒张期的时程，也缩短了钙瞬变时程。当刺激频率增加到1赫兹时，大多数HF心肌细胞的动作电位缩短，峰顶轮廓消失。心肌细胞的动作电位和钙瞬变时程与正常细胞无显著差异。然而，HF细胞的收缩-松弛周期显著延长(314+/-67ms，n=21，比221+/-38ms，n=46，平均+/-SD)，这表明HF心肌细胞的兴奋-收缩解偶联受损。结果表明，在心力衰竭犬分离的心肌细胞中，收缩异常和低刺激率下细胞内钙瞬变的异常表现为尖峰-穹顶结构。这种异常模式似乎是动作电位延长的结果。
Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca2+ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary micro-embolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca2+ transients by flue 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of con traction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca2+ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca2+ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 mu M) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca2+ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. Tn HE cardiomyocytes, the action potential and Ca2+ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation cycle was significantly longer in HF cells (314 +/- 67 ms, n = 21, vs. 221 +/- 38 ms, n = 46, mean +/- SD), indicating impaired excitation-contraction uncoupling in HF cardiomyocytes. The results show that, in cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca2+ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result from prolongation of the action potential.