Apneusis follows disruption of NMDA-type glutamate receptors in vagotomized ground squirrels.
The influences of N-methyl-D-aspartate (NMDA) type glutamate receptor antagonism, by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), on breathing pattern and ventilatory chemoresponses, were assessed in anaesthetized vagotomized spontaneously breathing golden-mantled ground squirrels, Spermophilus lateralis. MK-801 was administered by either bilateral pressure micro-injection into a region of the rostral dorsolateral pons, containing the medial and lateral Parabrachial and Kölliker-Fuse nuclei (the Parabrachial complex, PbC), or by systemic injection. Both treatments induced apneusis. These data indicate that functional NMDA receptor-mediated processes located within the PbC terminate inspiration and actively prevent apneusis in vagotomized ground squirrels. Although both hypercapnia and hypoxia stimulated breathing during the apneusis, the responses were generally slight. The breathing frequency component of the hypercapnic ventilatory response was completely eliminated supporting the hypothesis that the PbC is an integral component of the control network for CO(2) chemoreflex responses. Differences in the results of systemic versus PbC MK-801 illustrate that NMDA receptor-mediated processes outside the PbC do influence ventilation. Our data also show that such processes outside the PbC lengthen both inspiration and expiration in this species, slowing ventilation, and are necessary for the expression of the hypoxic ventilatory response.
Harris
Michael B
MB
Department of Physiology, Dartmouth Hitchcock Medical Center, Dartmouth College, Borwell Building Hinman box, 7700, One Medical Center Drive, Lebanon, NH 03756, USA. michael.b.harris@dartmouth.edu
Milsom
William K
WK
D000818:Animals; D001049:Apnea / Q000209:etiology* / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000009:adverse effects* / Q000494:pharmacology; D004333:Drug Administration Routes; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006935:Hypercapnia / Q000209:etiology; D000860:Hypoxia / Q000209:etiology; D007274:Injections, Intraperitoneal / Q000379:methods; D008297:Male; D008845:Microinjections / Q000379:methods; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D014628:Vagotomy / Q000009:adverse effects*; D014691:Ventilation / Q000379:methods; D014939:Work of Breathing / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate