George Washington University, Department of Pharmacology and Physiology, 2300 Eye St NW, Washington, DC 20037, USA.
J Neurophysiol. 2010 Oct;104(4):1841-8. doi: 10.1152/jn.00442.2010. Epub 2010 Aug 18.
Stimulation of the nasal mucosa by airborne irritants or water evokes a pronounced bradycardia accompanied by peripheral vasoconstriction and apnea. The dive response, which includes the trigeminocardiac reflex, is among the most powerful autonomic responses. These responses slow the heart rate and reduce myocardial oxygen consumption. Although normally cardioprotective, exaggeration of this reflex can be detrimental and has been implicated in cardiorespiratory diseases, including sudden infant death syndrome (SIDS). An essential component of the diving response and trigeminocardiac reflex is activation of the parasympathetic cardiac vagal neurons (CVNs) in the nucleus ambiguus that control heart rate. This study examined the involvement of cholinergic receptors in trigeminally evoked excitatory postsynaptic currents in CVNs in an in vitro preparation from rats. CVNs were identified using a retrograde tracer injected into the fat pads at the base of the heart. Application of the acetylcholinesterase inhibitor neostigmine significantly decreased the amplitude of glutamatergic neurotransmission to CVNs on stimulation of trigeminal fibers. Whereas nicotine did not have any effect on the glutamatergic responses, the muscarinic acetylcholine receptor (mAChR) agonist bethanechol significantly decreased the excitatory neurotransmission. Atropine, an mAChR antagonist, facilitated these responses indicating this trigeminally evoked brain stem pathway in vitro is endogenously inhibited by mAChRs. Tropicamide, an m4 mAChR antagonist, prevented the inhibitory action of the muscarinic agonist bethanechol. These results indicate that the glutamatergic synaptic neurotransmission in the trigeminally evoked pathway to CVNs is endogenously inhibited in vitro by m4 mAChRs.
空气传播的刺激物或水刺激鼻黏膜会引起明显的心动过缓，同时伴有外周血管收缩和呼吸暂停。潜水反应包括三叉心脏反射，是最强大的自主反应之一。这些反应会降低心率并减少心肌耗氧量。尽管通常对心脏有保护作用，但这种反射的过度夸大可能有害，并与包括婴儿猝死综合征（SIDS）在内的心肺疾病有关。潜水反应和三叉心脏反射的一个重要组成部分是激活控制心率的疑核中的副交感神经心脏迷走神经元（CVN）。这项研究检查了胆碱能受体在体外大鼠制备物中三叉神经诱发的 CVN 兴奋性突触后电流中的作用。使用逆行示踪剂将 CVN 鉴定为注入心脏底部脂肪垫。乙酰胆碱酯酶抑制剂新斯的明的应用显著降低了三叉神经纤维刺激时 CVN 中谷氨酸能神经传递的幅度。虽然尼古丁对谷氨酸能反应没有任何影响，但毒蕈碱乙酰胆碱受体（mAChR）激动剂氨甲酰胆碱显著降低了兴奋性神经传递。阿托品，一种 mAChR 拮抗剂，促进了这些反应，表明这种体外三叉神经脑干通路内源性受到 mAChRs 的抑制。托吡卡胺，一种 m4 mAChR 拮抗剂，阻止了毒蕈碱激动剂氨甲酰胆碱的抑制作用。这些结果表明，在体外，三叉神经诱发的 CVN 途径中的谷氨酸能突触神经传递被 m4 mAChRs 内源性抑制。
