Griffioen Kathleen J S, Venkatesan Priya, Huang Zheng-Gui, Wang Xin, Bouairi Evguenia, Evans Cory, Gold Allison, Mendelowitz David
Department of Pharmacology and Physiology, George Washington University, 2300 Eye Street N.W., Washington, DC 20037, USA.
Brain Res. 2004 May 8;1007(1-2):109-15. doi: 10.1016/j.brainres.2004.02.010.
Fentanyl citrate is a synthetic opiate analgesic often used clinically for neonatal anesthesia. Although fentanyl significantly depresses heart rate, the mechanism of inducing bradycardia remains unclear. One possible site of action is the cardioinhibitory parasympathetic vagal neurons in the nucleus ambiguus (NA), from which originates control of heart rate and cardiac function. Inhibitory synaptic activity to cardiac vagal neurons is a major determinant of their activity. Therefore, the effect of fentanyl on GABAergic neurotransmission to parasympathetic cardiac vagal neurons was studied using whole-cell patch clamp electrophysiology. Application of fentanyl induced a reduction in both the frequency and amplitude of GABAergic IPSCs in cardiac vagal neurons. This inhibition was mediated at both pre- and postsynaptic sites as evidenced by a dual decrease in the frequency and amplitude of spontaneous miniature IPSCs. Application of the selective micro-antagonist CTOP abolished the fentanyl-mediated inhibition of GABAergic IPSCs. These results demonstrate that fentanyl acts on micro-opioid receptors on cardiac vagal neurons and neurons preceding them to reduce GABAergic neurotransmission and increase parasympathetic activity. The inhibition of GABAergic effects may be one mechanism by which fentanyl induces bradycardia.
枸橼酸芬太尼是一种合成阿片类镇痛药，临床上常用于新生儿麻醉。尽管芬太尼会显著降低心率，但其诱发心动过缓的机制仍不清楚。一个可能的作用部位是疑核（NA）中的心脏抑制性副交感迷走神经元，心率和心脏功能的控制由此起源。对心脏迷走神经元的抑制性突触活动是其活动的主要决定因素。因此，使用全细胞膜片钳电生理学方法研究了芬太尼对副交感心脏迷走神经元GABA能神经传递的影响。应用芬太尼可导致心脏迷走神经元中GABA能抑制性突触后电流（IPSCs）的频率和幅度降低。自发性微小IPSCs的频率和幅度双重降低证明，这种抑制作用在突触前和突触后位点均有介导。应用选择性微拮抗剂CTOP消除了芬太尼介导的对GABA能IPSCs的抑制作用。这些结果表明，芬太尼作用于心脏迷走神经元及其之前的神经元上的微阿片受体，以减少GABA能神经传递并增加副交感神经活动。对GABA能效应的抑制可能是芬太尼诱发心动过缓的一种机制。
