Haji Akira, Ohi Yoshiaki, Tsunekawa Saori
Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya 464-8650, Japan.
Neuropharmacology. 2008 Jun;54(7):1120-7. doi: 10.1016/j.neuropharm.2008.03.003. Epub 2008 Mar 16.
Cough reflex is characterized by a large expulsive phase for expelling the mucus or particles from the airway. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) mechanisms in the expulsive phase of cough reflex using decerebrate and paralyzed cats. A fictive cough was induced by repetitive stimulation of the superior laryngeal nerve, which was characterized by an increased inspiratory discharge in the phrenic nerve (the stage 1 of fictive cough; SC1) and large spindle-shaped discharge in the iliohypogastric nerve (the stage 2 of fictive cough; SC2). Intravenous injection of an antagonist of NMDA receptors, dizocilpine (0.1mg/kg), increased the threshold intensity of stimulation for inducing a fictive cough. The SC2 iliohypogastric response was more vulnerable to dizocilpine than the SC1 phrenic response. Membrane potential of augmenting expiratory (aug-E) neurons was recorded from the caudal ventral respiratory group. Aug-E neurons showed a large depolarization with a high frequency discharge during the SC2 in major cases (n=35) and hyperpolarization in minor cases (n=6). Dizocilpine inhibited the occurrence of these SC2 responses of aug-E neurons without any effect on the basal respiratory fluctuations of membrane potential. This drug had no significant effect on waves of excitatory and inhibitory postsynaptic potentials evoked in aug-E neurons by single pulse stimulation of the SLN. The present results demonstrated that NMDA mechanisms contribute preferentially to the expulsive phase response in aug-E neurons during fictive cough reflex.
咳嗽反射的特点是有一个较大的呼气阶段，用于将气道中的黏液或颗粒排出。本研究利用去大脑并麻痹的猫，研究了N-甲基-D-天冬氨酸（NMDA）机制在咳嗽反射呼气阶段中的作用。通过重复刺激喉上神经诱发假咳嗽，其特征为膈神经吸气放电增加（假咳嗽第1阶段；SC1）以及髂腹下神经出现大的纺锤形放电（假咳嗽第2阶段；SC2）。静脉注射NMDA受体拮抗剂地卓西平（0.1mg/kg）可提高诱发假咳嗽的刺激阈值强度。与SC1膈神经反应相比，SC2髂腹下神经反应对地卓西平更敏感。从尾侧腹侧呼吸组记录增强呼气（aug-E）神经元的膜电位。在大多数情况下（n=35），aug-E神经元在SC2期间表现出大的去极化并伴有高频放电，少数情况下（n=6）表现为超极化。地卓西平抑制了aug-E神经元这些SC2反应的发生，而对膜电位的基础呼吸波动没有任何影响。该药物对喉上神经单脉冲刺激诱发的aug-E神经元兴奋性和抑制性突触后电位波形没有显著影响。目前的结果表明，在假咳嗽反射期间，NMDA机制优先参与aug-E神经元的呼气阶段反应。
