Connelly C A, Otto-Smith M R, Feldman J L
Department of Physiological Science, University of California, Los Angeles 90024-1527.
Brain Res. 1992 Nov 20;596(1-2):99-110. doi: 10.1016/0006-8993(92)91537-o.
The role of N-methyl-D-aspartate (NMDA) receptor-channel activation in the production of respiratory pattern was studied by administration of the NMDA receptor-channel blocker (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801, 1-3 mg/kg, i.v.) to anesthetized adult rats. This dose of MK-801 blocked the excitatory effects of NMDA (applied iontophoretically) on brainstem respiratory neurons. The predominant respiratory response to systemic MK-801 administration was an increase in inspiratory duration and a decrease in amplitude of diaphragm electromyogram and phrenic nerve discharge. Effects on inspiratory timing and amplitude were most pronounced when the rats were vagotomized. Significant changes in arterial blood gases and pH after systemic MK-801 administration in spontaneously breathing rats (vagi intact or cut) indicated that ventilation was depressed by NMDA receptor-channel antagonism. Respiratory timing changes in response to systemic MK-801 administration differed between two rat strains studied. Breathing patterns resembling apneusis, i.e., with irregular inspiratory durations prolonged 2- to 30-fold, occurred in 60% of the vagotomized, spontaneously breathing Sprague-Dawley rats and none of the Wistar rats. Thus, the breathing pattern in Sprague-Dawley rats is more sensitive to interference with NMDA-mediated mechanisms. We propose that respiratory pattern generation and transmission of rhythmic respiratory drive are mediated by synergistic activation of NMDA and non-NMDA receptors at brainstem and spinal cord sites.
通过向成年麻醉大鼠静脉注射N-甲基-D-天冬氨酸（NMDA）受体通道阻滞剂（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸氢盐（MK-801，1-3mg/kg），研究了NMDA受体通道激活在呼吸模式产生中的作用。该剂量的MK-801阻断了NMDA（通过离子电泳施加）对脑干呼吸神经元的兴奋作用。全身给予MK-801后的主要呼吸反应是吸气持续时间增加，膈肌肌电图和膈神经放电幅度减小。当大鼠迷走神经切断时，对吸气时间和幅度的影响最为明显。在自主呼吸大鼠（迷走神经完整或切断）中全身给予MK-801后，动脉血气和pH值发生显著变化，表明NMDA受体通道拮抗作用会抑制通气。在研究的两种大鼠品系中，全身给予MK-801后的呼吸时间变化有所不同。60%的迷走神经切断、自主呼吸的Sprague-Dawley大鼠出现类似窒息的呼吸模式，即吸气持续时间不规则延长2至30倍，而Wistar大鼠无一出现。因此，Sprague-Dawley大鼠的呼吸模式对NMDA介导机制的干扰更敏感。我们提出，呼吸模式的产生和节律性呼吸驱动的传递是由脑干和脊髓部位的NMDA和非NMDA受体的协同激活介导的。
