The State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University Shanghai Medical College, Shanghai, PR China.
Neuroscience. 2012 Apr 5;207:78-87. doi: 10.1016/j.neuroscience.2012.01.047. Epub 2012 Feb 6.
The vagus nerves supply the major cholinergic tone to airway smooth muscles physiologically and play critical roles in the genesis of airway hyperreactivity under some pathological conditions. Postganglionic airway cholinergic tone relies largely on the ongoing activity of medullary airway vagal preganglionic neurons (AVPNs), of which the tracheobronchial-projecting ones are primarily located in the external formation of the nucleus ambiguus (eNA). AVPNs are regulated by 5-HT, and 5-HT(1A/7) and 5-HT(2) receptors have been indicated to be involved. But the mechanisms at synaptic level are unknown. In the present study, tracheobronchial-projecting AVPNs (T-AVPNs) were retrogradely labeled from the trachea wall; fluorescently labeled T-AVPNs in the eNA were recorded with whole-cell voltage patch clamp; and the effects of 5-HT(1A/7) receptor agonist (±)-8-Hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT) (1 μmol L(-1)) and 5-HT(2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10 μmol L(-1)) on the synaptic inputs were examined. 8-OH-DPAT significantly inhibited the GABAergic and glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) of T-AVPNs in both the frequency and amplitude but had no effect on the GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs). The 8-OH-DPAT inhibition of the GABAergic and glycinergic sIPSCs was prevented by 5-HT(1A/7) receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY-100635) (1 μmol L(-1)). 8-OH-DPAT had no effect on the glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) and caused no alterations in the baseline current and input resistance of T-AVPNs. DOI had no effect on any types of the synaptic inputs of T-AVPNs. These results suggest that 5-HT(1A/7) receptor agonist causes "disinhibition" of T-AVPNs, which might, in part, account for the reflex increase of airway resistance.
迷走神经为气道平滑肌提供主要的胆碱能张力，在某些病理条件下，在气道高反应性的产生中起关键作用。节后气道胆碱能张力主要依赖于延髓气道迷走节前神经元（AVPN）的持续活动，其中气管支气管投射型 AVPN 主要位于疑核的外部形成（eNA）。AVPN 受 5-HT 调节，并且已经表明 5-HT（1A/7）和 5-HT（2）受体参与其中。但是，突触水平的机制尚不清楚。在本研究中，从气管壁逆行标记气管支气管投射型 AVPN（T-AVPN）；用全细胞膜片钳记录 eNA 中荧光标记的 T-AVPN；并检查 5-HT（1A/7）受体激动剂（±）-8-羟基-2-（二丙基氨基）四氢呋喃盐酸盐（8-OH-DPAT）（1μmol L（-1））和 5-HT（2）受体激动剂 1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）（10μmol L（-1））对突触传入的影响。8-OH-DPAT 显著抑制 T-AVPN 的 GABA 能和甘氨酸能自发性抑制性突触后电流（sIPSCs）的频率和幅度，但对 GABA 能和甘氨酸能微小抑制性突触后电流（mIPSCs）没有影响。5-HT（1A/7）受体拮抗剂 N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-2-吡啶基环己烷甲酰胺马来酸盐（WAY-100635）（1μmol L（-1））可防止 8-OH-DPAT 对 GABA 能和甘氨酸能 sIPSCs 的抑制。8-OH-DPAT 对谷氨酸能自发性兴奋性突触后电流（sEPSCs）没有影响，并且对 T-AVPN 的基线电流和输入电阻没有改变。DOI 对 T-AVPN 的任何类型的突触传入均无影响。这些结果表明，5-HT（1A/7）受体激动剂导致 T-AVPN 产生“去抑制”，这可能部分解释了气道阻力的反射性增加。
