NMDA as well as non-NMDA receptors in phrenic nucleus mediate respiratory effects of carotid chemoreflex
Chitravanshi, V.C.; Sapru, H.N.
American Journal of Physiology 272(1 Pt 2): R302-R310
1997
ISSN/ISBN: 0002-9513 PMID: 9039022 Document Number: 473334
An in vivo model was used to identify the transmitter/receptor mechanisms in the phrenic nucleus that mediate carotid chemoreceptor responses. Adult male Wistar rats, anesthetized with urethan, were fixed in a stereotaxic instrument, and the blood pressure and heart rate were monitored. The rats were immobilized and artificially ventilated to maintain the end-tidal CO-2 at 4.5-5%. The vagus nerves were bilaterally sectioned, and a pneumothorax was produced. Activity was recorded from one of the phrenic nerves. The spinal cord was exposed from C-1 to T-1 vertebral level. The dorsal and ventral rootlets of spinal nerves C-3, C-5, and C-6, ipsilateral to the phrenic nerve from which electrical activity was recorded, were sectioned; the dorsal and ventral roots of spinal nerve C-4 were left intact. Thus the phrenic nerve bursts recorded in this preparation represented output from a portion of the phrenic nucleus located in the ipsilateral C-4 spinal segment. Carotid chemoreceptor stimulation by N-2 inhalation increased the amplitude as well as the frequency of phrenic nerve bursts. Microinjections (50 nl) of a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist (D(-)-2-amino-7-phosphonoheptanoic acid, AP-7, 50-100 mM) into the phrenic nucleus decreased the N-2-induced increase in amplitude, but not the frequency, of phrenic nerve bursts. Likewise microinjections of a specific non-NMDA receptor antagonist (1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamide, NBQX, 0.5-1 mM) into the phrenic nucleus decreased the N-2-induced increase in phrenic nerve burst amplitude. When AP-7 and NBQX were microinjected into the phrenic nucleus sequentially within an interval of 5 min, a drastic reduction in the N-2-induced increase in phrenic nerve burst amplitude was observed. These observations suggest that both NMDA and non-NMDA receptors located in the phrenic nucleus are involved in the mediation of phrenic nerve responses to the carotid chemoreceptor stimulation.