Retrotrapezoid nucleus glutamate receptors: control of CO2-sensitive phrenic and sympathetic output.
In decerebrate cats, we asked whether endogenous glutamate in the region of the retrotrapezoid nucleus (RTN) was involved in the control of CO2-sensitive phrenic and phrenic-related sympathetic output and, if so, which type of glutamate receptor was predominant. We made unilateral 10-nl injections into the RTN of the nonspecific glutamate receptor antagonist kynurenic acid (100 and 250 mM), the N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 1 and 10 mM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX; 1 and 10 mM), and the inactive kynurenic acid analogue xanthurenic acid (100 mM). Each antagonist resulted in a significant dose-dependent decrease in the amplitude of the integrated phrenic nerve signal (PNA) over 30 min (CNQX > AP5 > kynurenic acid). The duration of the phrenic cycle was also decreased because of a shortening of expiratory time (CNQX > kynurenic acid > AP5). All three antagonists significantly decreased the initial slope of the PNA response to increased CO2 by 70-80% with no clear distinction in efficacy. The amplitude of the respiratory-related integrated cervical sympathetic nerve signal (SNA) was significantly decreased after kynurenic acid and CNQX but not AP5. In each case, the decrease in respiratory-related SNA accompanied a decrease in PNA and, at high levels of CO2, the decrease in respiratory-related SNA was greater than that of PNA. Endogenous glutaminergic input to neurons in the RTN via both NMDA and non-NMDA receptors is involved in the control of eucapneic PNA and timing, PNA-related SNA, and the response to increased CO2.
Nattie
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EE
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001.
Gdovin
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M
Li
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide; D002415:Cats; D003655:Decerebrate State / Q000503:physiopathology; D004594:Electrophysiology; D005260:Female; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
D011810:Quinoxalines; D017470:Receptors, Glutamate; D002245:Carbon Dioxide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid