Acetylcholine modulates I(f) and IK(ACh) via different pathways in rabbit sino-atrial node cells.
Acetylcholine modulates I(f) and IK(ACh) via different pathways in rabbit sino-atrial node cells.
复制标题
乙酰胆碱通过不同途径调节兔窦房结细胞中的 I(f) 和 IK(ACh)。
DOI：
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发表时间：
1997
影响因子：
5
通讯作者：
J. Lenfant
中科院分区：
文献类型：
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作者：
B. Renaudon;P. Bois;J. Bescond;J. Lenfant
本研究的目的是检查是否有必要直接G蛋白通路来解释乙酰胆碱（ACh）对心脏起搏电流（I（f））的抑制。用细胞贴附和外向的宏膜片法同时测定了离体兔心窦房结细胞的起搏电流和毒蕈碱钾电流的自发波动（IK（ACh））。将1 μ M ACh加入到浴溶液中，比较其对I（f）和IK（ACh）的影响，已知IK通过直接G蛋白机制激活。在存在细胞质底物的细胞贴附构型中，ACh通过开放概率曲线的负向移动（7.6 +/- 0.3 mV）抑制I（f）。乙酰胆碱从来没有引起修改自发开放的毒蕈碱钾通道。这些结果表明，ACh加入到外部解决方案是无法调制IK（ACh）记录在膜界定的模式，通过G蛋白途径。ACh对I（f）的抑制作用与第二信使活性的改变有关。在由外向外的条件下，将鸟苷三磷酸（GTP）加入移液器溶液中。ACh使IK（ACh）波动的方差从1.66 +/- 0.50 pA 2增加到6.60 +/- 2.05 pA 2（-120 mV）。表明直接G蛋白作用。ACh对I（f）无影响。它的结论是，在SA结细胞中，I（f）的毒蕈碱受体的调节不涉及直接的G-蛋白通路。ACh通过一种可能涉及细胞内cAMP产生减少的机制抑制I（f）。
The aim of the present study was to examine whether a direct G-protein pathway was necessary to explain the depression of the cardiac pacemaker current (I(f)) by acetylcholine (ACh). Pacemaker current and spontaneous fluctuations of muscarinic K+ current (IK(ACh)) were simultaneously measured in sino-atrial (SA) node cells isolated from rabbit hearts, using cell-attached and outside-out macro-patches. The effects of 1 microM ACh, added to the bathing solution, were compared on I(f) and on IK(ACh), known to be activated via a direct G-protein mechanism. In a cell-attached configuration where cytoplasmic substrates were present, ACh depressed I(f) by a negatively directed shift of the open probability curve of 7.6 +/- 0.3 mV. ACh never induced modifications in spontaneous openings of muscarinic K+ channels. These results indicate that ACh added to the external solution is unable to modulate IK(ACh) recorded in the membrane-delimited mode, via a G-protein pathway. The ACh depressing effect on I(f) is related to changes in second messenger activity. In outside-out conditions, with guanosine triphosphate (GTP) added to the pipette solution. ACh increased the variance of IK(ACh) fluctuations from 1.66 +/- 0.50 pA2 to 6.60 +/- 2.05 pA2 (at -120 mV). indicating direct G-protein action. ACh had no effect on I(f). It is concluded that in SA node cells, the regulation of I(f) by muscarinic receptors does not involve a direct G-protein pathway. ACh depresses I(f) by a mechanism that probably implicates reduction of intracellular cAMP production.