Pietsch P, Hunger T, Braun M, Roediger A, Baumann G, Felix S B
Medizinische Klinik I, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Germany.
J Cardiovasc Pharmacol. 1998 May;31(5):758-63. doi: 10.1097/00005344-199805000-00015.
We investigated the effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) on intracellular Ca2+ concentration ([Ca2+]i) and cell length in isolated and field-stimulated rat cardiomyocytes. [Ca2+]i and cell length of field-stimulated cells were determined simultaneously by confocal laser scan microscopy by using the fluorescent Ca2+ dye Fluo-3. PAF (10(-12)-10(-8) M) inhibited systolic [Ca2+]i increase in a time- and concentration-dependent manner. Maximal effects were observed after an incubation time of 6-8 min, resulting in a 17% (10(-12) M), 41% (10(-10) M), and 52% (10(-8) M PAF) inhibition of systolic [Ca2+]i increase. A time- and concentration-dependent decrease in simultaneously measured cell shortening also was demonstrated. Cell shortening was inhibited by 10% (10(-12) M), 32% (10(-10) M), and 50% (10(-8) M) after an incubation time of 8 min. The effects of PAF could be antagonized by the PAF-receptor antagonist WEB 2170. These data demonstrate that PAF receptor-dependently induces a negative inotropic effect, which is correlated with a decrease in systolic [Ca2+]i and is most likely not due to a decrease in myofilament sensitivity.
我们研究了血小板活化因子(PAF,1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱)对分离的和经场刺激的大鼠心肌细胞内钙离子浓度([Ca2+]i)及细胞长度的影响。通过共聚焦激光扫描显微镜使用荧光钙离子染料Fluo-3同时测定经场刺激细胞的[Ca2+]i和细胞长度。PAF(10^(-12)-10^(-8) M)以时间和浓度依赖性方式抑制收缩期[Ca2+]i升高。孵育6-8分钟后观察到最大效应,导致收缩期[Ca2+]i升高分别受到17%(10^(-12) M)、41%(10^(-10) M)和52%(10^(-8) M PAF)的抑制。同时测量的细胞缩短也呈现出时间和浓度依赖性降低。孵育8分钟后,细胞缩短分别受到10%(10^(-12) M)、32%(10^(-10) M)和50%(10^(-8) M)的抑制。PAF的作用可被PAF受体拮抗剂WEB 2170拮抗。这些数据表明,PAF受体依赖性地诱导负性肌力作用,这与收缩期[Ca2+]i降低相关,且很可能不是由于肌丝敏感性降低所致。