Li Y H, Rozanski G J
Department of Internal Medicine (Cardiology), University of Nebraska College of Medicine, Omaha 68189-4575.
Cardiovasc Res. 1993 Mar;27(3):525-30. doi: 10.1093/cvr/27.3.525.
To determine whether cytokines alter the electrical properties of heart cells, the effects of human recombinant interleukin-1 beta (IL-1) were examined in excised tissues and dissociated myocytes from guinea pig ventricles.
In a first series of experiments, transmembrane potentials were recorded from isolated papillary muscles superfused with 1 ng.ml-1 IL-1 in the absence and presence of blockers of arachidonic acid metabolism. Secondly, to examine the ionic mechanisms underlying the response to IL-1, ventricular myocytes were dissociated from collagenase perfused hearts and studied using the whole cell configuration of the patch clamp technique under conditions designed to isolate the L-type Ca2+ current (ICa).
In excised papillary muscles, IL-1 significantly prolonged action potential duration (measured at 90% repolarisation) by 24.2(SEM 2.2) ms and effective refractory period by 22.9(2.3) ms (both p < 0.001; n = 44). Other measured variables were not affected. Treatment of muscles with cyclo-oxygenase inhibitors, indomethacin (1 x 10(-5) M) or acetyl salicylic acid (2 x 10(-4) M), abolished the prolongation of action potential duration elicited by IL-1. However, the effects of IL-1 were also blocked by the lipoxygenase inhibitor nordihydroguaiaretic acid (2 x 10(-5) M) or by treating tissues with the leukotriene receptor blocker, ICI198615 (1 x 10(-8) M). In isolated myocytes, 1 ng.ml-1 IL-1 increased ICa density in 44 of 78 cells by 33.6(7.5)% [11.7(0.6) v 14.6(0.7) pA.pF-1; p < 0.001] during voltage steps from -40 to 0 mV.
IL-1 modifies electrical properties of cardiac cells via lipid second messengers generated by cyclo-oxygenase and lipoxygenase pathways. Voltage clamp analyses suggest that these effects are mediated, at least in part, by changes in the conductance of calcium channels.
为了确定细胞因子是否会改变心脏细胞的电特性，我们在豚鼠心室的离体组织和分离的心肌细胞中检测了重组人白细胞介素-1β（IL-1）的作用。
在第一系列实验中，在不存在和存在花生四烯酸代谢阻滞剂的情况下，记录灌流1 ng.ml-1 IL-1的离体乳头肌的跨膜电位。其次，为了研究对IL-1反应的离子机制，从用胶原酶灌流的心脏中分离心室肌细胞，并在旨在分离L型钙电流（ICa）的条件下，使用膜片钳技术的全细胞模式进行研究。
在离体乳头肌中，IL-1使动作电位时程（在复极化90%时测量）显著延长24.2（标准误2.2）ms，有效不应期延长22.9（2.3）ms（两者p<0.001；n=44）。其他测量变量未受影响。用环氧化酶抑制剂吲哚美辛（1×10-5 M）或乙酰水杨酸（2×10-4 M）处理肌肉，可消除IL-1引起的动作电位时程延长。然而，IL-1的作用也被脂氧合酶抑制剂去甲二氢愈创木酸（2×10-5 M）或用白三烯受体阻滞剂ICI198615（1×10-8 M）处理组织所阻断。在分离的心肌细胞中，在从-40到0 mV的电压阶跃期间，1 ng.ml-1 IL-1使78个细胞中的44个细胞的ICa密度增加33.6（7.5）%[11.7（0.6）对14.6（0.7）pA.pF-1；p<0.001]。
IL-1通过环氧化酶和脂氧合酶途径产生的脂质第二信使改变心脏细胞的电特性。电压钳分析表明，这些作用至少部分是由钙通道电导的变化介导的。
