Zhang B X, Ma X, McConnell B K, Damron D S, Bond M
Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
Circ Res. 1996 Jul;79(1):94-102. doi: 10.1161/01.res.79.1.94.
Extracellular ATP is an important neurotransmitter that modulates cardiac function by activation of purinergic receptors. In this study, the effect of P2 purinergic receptor activation on contractions and on [Ca2+]i was investigated in adult rat ventricular myocytes. Fura 2 was used to measure [Ca2+]i, and video edge detection was used to measure contraction. Superfusion of 2-methylthio-adenosine-5'-triphosphate (2-M-S-ATP) over quiescent myocytes induced oscillations in contraction and in [Ca2+]i. The frequency of the oscillatory contractions increased with increasing concentrations of 2-M-S-ATP, but the amplitude of contractions varied from cell to cell and was independent of the concentration of 2-M-S-ATP. During electrical stimulation, activation of purinergic receptors in myocytes potentiated the amplitude of contraction and induced arrhythmias. In populations of quiescent myocytes, the plateau phase of the [Ca2+]i signal evoked by 2-M-S-ATP could be shown to represent summed oscillations in [Ca2+]i in individual cells. Pretreatment of quiescent myocytes with thapsigargin or caffeine reduced or abolished the oscillations in contractions and in [Ca2+]i triggered by 2-M-S-ATP, indicating a dependence of the oscillations on uptake and release of Ca2+ by the sarcoplasmic reticulum. These data demonstrate the novel phenomenon that activation of purinergic receptors in quiescent myocytes stimulates oscillations in [Ca2+]i and contraction. In electrically stimulated myocytes, activation of purinergic receptors triggers oscillatory contractions and potentiates the amplitude of electrically triggered contractions.
细胞外ATP是一种重要的神经递质，可通过激活嘌呤能受体来调节心脏功能。在本研究中，我们研究了P2嘌呤能受体激活对成年大鼠心室肌细胞收缩及细胞内钙离子浓度（[Ca2+]i）的影响。采用Fura 2测量[Ca2+]i，并利用视频边缘检测技术测量收缩情况。用2-甲硫基腺苷-5'-三磷酸（2-M-S-ATP）灌注静息态的心肌细胞，可诱导收缩及[Ca2+]i产生振荡。振荡性收缩的频率随2-M-S-ATP浓度的增加而升高，但收缩幅度在细胞之间存在差异，且与2-M-S-ATP的浓度无关。在电刺激过程中，心肌细胞中嘌呤能受体的激活增强了收缩幅度并诱发心律失常。在静息态心肌细胞群体中，2-M-S-ATP诱发的[Ca2+]i信号的平台期可显示为单个细胞中[Ca2+]i的叠加振荡。用毒胡萝卜素或咖啡因预处理静息态心肌细胞，可减少或消除由2-M-S-ATP触发的收缩及[Ca2+]i的振荡，这表明振荡依赖于肌浆网对钙离子的摄取和释放。这些数据证明了一种新现象，即静息态心肌细胞中嘌呤能受体的激活可刺激[Ca2+]i及收缩产生振荡。在电刺激的心肌细胞中，嘌呤能受体的激活触发振荡性收缩，并增强电触发收缩的幅度。
