Gao Xiuping, Zhao Lei, Zhuang Jianguo, Zang Na, Xu Fadi
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA
FASEB J. 2017 Oct;31(10):4325-4334. doi: 10.1096/fj.201700163R. Epub 2017 Jun 14.
Maternal cigarette smoke, including prenatal nicotinic exposure (PNE), is responsible for sudden infant death syndrome (SIDS). The fatal events of SIDS are characterized by severe bradycardia and life-threatening apneas. Although activation of transient receptor potential vanilloid 1 (TRPV1) of superior laryngeal C fibers (SLCFs) could induce bradycardia and apnea and has been implicated in SIDS pathogenesis, how PNE affects the SLCF-mediated cardiorespiratory responses remains unexplored. Here, we tested the hypothesis that PNE would aggravate the SLCF-mediated apnea and bradycardia up-regulating TRPV1 expression and excitation of laryngeal C neurons in the nodose/jugular (N/J) ganglia. To this end, we compared the following outcomes between control and PNE rat pups at postnatal days 11-14: ) the cardiorespiratory responses to intralaryngeal application of capsaicin (10 µg/ml, 50 µl), a selective stimulant for TRPV1 receptors, in anesthetized preparation; ) immunoreactivity and mRNA of TRPV1 receptors of laryngeal sensory C neurons in the N/J ganglia retrogradely traced by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; and ) TRPV1 currents and electrophysiological characteristics of these neurons by using whole-cell patch-clamp technique Our results showed that PNE markedly prolonged the apneic response and exacerbated the bradycardic response to intralaryngeal perfusion of capsaicin, which was associated with up-regulation of TRPV1 expression in laryngeal C neurons. In addition, PNE increased the TRPV1 currents, depressed the slow delayed rectifier potassium currents, and increased the resting membrane potential of these neurons. Our results suggest that PNE is capable of aggravating the SLCF-mediated apnea and bradycardia through TRPV1 sensitization and neuronal excitation, which may contribute to the pathogenesis of SIDS.-Gao, X., Zhao, L., Zhuang, J., Zang, N., Xu, F. Prenatal nicotinic exposure prolongs superior laryngeal C-fiber-mediated apnea and bradycardia through enhancing neuronal TRPV1 expression and excitation.
母亲吸烟，包括产前尼古丁暴露（PNE），是婴儿猝死综合征（SIDS）的病因。SIDS的致命事件的特征是严重心动过缓和危及生命的呼吸暂停。虽然喉上C纤维（SLCF）的瞬时受体电位香草酸受体1（TRPV1）的激活可诱发心动过缓和呼吸暂停，并与SIDS发病机制有关，但PNE如何影响SLCF介导的心肺反应仍未得到探索。在此，我们测试了以下假设：PNE会通过上调TRPV1表达和激发结状/颈静脉（N/J）神经节中的喉C神经元，加重SLCF介导的呼吸暂停和心动过缓。为此，我们比较了出生后11-14天的对照和PNE大鼠幼崽之间的以下结果：）在麻醉制剂中，对喉内应用辣椒素（10μg/ml，50μl）（一种TRPV1受体的选择性刺激剂）的心肺反应；）用1,1'-二辛基-3,3,3',3'-四甲基吲哚碳菁高氯酸盐逆行追踪的N/J神经节中喉感觉C神经元的TRPV1受体的免疫反应性和mRNA；以及）通过使用全细胞膜片钳技术检测这些神经元的TRPV1电流和电生理特征。我们的结果表明，PNE显著延长了对喉内灌注辣椒素的呼吸暂停反应，并加剧了心动过缓反应，这与喉C神经元中TRPV1表达上调有关。此外，PNE增加了TRPV1电流，抑制了缓慢延迟整流钾电流，并增加了这些神经元的静息膜电位。我们的结果表明，PNE能够通过TRPV1敏化和神经元兴奋加重SLCF介导的呼吸暂停和心动过缓，这可能有助于SIDS的发病机制。-高X，赵L，庄J，臧N，徐F。产前尼古丁暴露通过增强神经元TRPV1表达和兴奋延长喉上C纤维介导的呼吸暂停和心动过缓
