Mechanism of acetylcholine action on pacemaker current (i(f)) in canine Purkinje fibers.
Mechanism of acetylcholine action on pacemaker current (i(f)) in canine Purkinje fibers.
复制标题
乙酰胆碱对犬浦肯野纤维起搏器电流（i（f））的作用机制。
DOI：
10.1007/bf00374474
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Cohen,IS
中科院分区：
文献类型：
--
作者：
Chang,F;Cohen,IS
我们最近在犬浦肯野纤维中报道，乙酰胆碱（ACh）可逆转β-肾上腺素能刺激诱导的起搏电流（If）的正电压偏移，而其本身无直接作用[3]。我们现在已经研究了这种效果的乙酰胆碱对环磷酸腺苷（cAMP）级联反应的更详细。我们发现，加入0.5-1 mM的cAMP类似物（8-chlorophenylthiocAMP）可使f的振幅增加，这种作用不被1 μM ACh逆转，表明ACh的作用先于cAMP。然后，我们研究了控制细胞内cAMP浓度的步骤。用100 μM异丁基-1-甲基黄嘌呤（IBMX）抑制磷酸二酯酶，然而，这种作用被ACh逆转。最后，我们研究了佛司可林的作用，腺苷酸环化酶的直接激活剂，可以逆转乙酰胆碱。Forskolin（10-20 μM）可使上述作用增强，ACh（1 μM）可部分逆转Forskolin的上述作用。这些结果表明，在犬浦肯野纤维中，ACh通过减少cAMP的产生来逆转β-肾上腺素能药物对NF的正性作用。
We have recently reported in canine Purkinje fibers that acetylcholine (ACh) can reverse the positive voltage shift of the pacemaker current (if) induced byβ-adrenergic stimulation while having no direct action of its own [3]. We have now investigated this effect of ACh on the cyclic adenosine monophosphate (cAMP) cascade in more detail. We find that addition of a membrane permeable analogue of cAMP (8-chlorophenylthio cAMP), 0.5–1 mM, increased the amplitude ofif.This action was not reversed by 1 μM ACh, implying that ACh acts at a step prior to cAMP action. We then looked at the steps controlling intracellular concentration of cAMP. Inhibiting the phosphodiesterase with 100 μM isobutyl-1-methylxanthine (IBMX) increasedif. This action, however, was reversed by ACh. Finally we investigated whether the action of forskolin, a direct activator of adenylyl cyclase, could be reversed by ACh. Forskolin (10–20 μM) increasedif, and ACh at 1 μM partially reversed this action of forskolin. These results suggest that, in canine Purkinje fibers, ACh reverses the positive action ofβ-adrenergic agents onifvia a decrease in cAMP production.