NMDA RECEPTOR-MEDIATED TRANSMISSION OF CAROTID-BODY CHEMORECEPTOR INPUT TO EXPIRATORY BULBOSPINAL NEURONS IN DOGS

1. This study tested the hypothesis that excitatory amino acid recepto rs mediate the excitatory response of expiratory bulbospinal neurones to carotid body chemoreceptor inputs. 2. Studies mere carried out in t hiopental sodium anaesthetized, paralysed, ventilated, vagotomized dog s. 3. Brisk, short-duration chemoreceptor activation nas produced by b ilateral bolus injections of CO2-saturated saline (P-Co2 > 700 mmHg) i nto the autoperfused carotid arteries. A pressurized-reservoir-solenoi d valve system was used to deliver the CO2 bolus injections just prior to tile onset of the neural expiratory phase, as determined from the phrenic neurogram, about once per minute. 4. Multibarrelled micropipet tes mere used to record neuronal unit activity and deliver neurotransm itter agents. Net responses of expiratory bulbospinal neurones to peri pheral chemoreceptor activation were determined by subtracting the mea n discharge frequencies (F-n) during three control expiratory cycles f rom the F-n during administration of a CO2 test bolus. The role of exc itatory amino acid receptors in mediating this response was determined by comparing the baseline and bolus expiratory neuronal F-n before, d uring and after the pressure microejection of the NMDA receptor antago nist 2-amino-5-phosphonovalerate (AP5) or the non-NMDA receptor antago nist dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline (NBQX). Ejecti on rates of AP5 and NBQX were measured by monitoring the movement of t he pipette meniscus. 5. AP5 reduced F-n during both the control and bo lus cycles, as well as reducing the change in F-n between control and bolus cycles. NBQX had no effect on either baseline or bolus responses . 6. AP5 did not prevent excitation of expiratory bullospinal neurones by AMPA. Coadministration of AMPA with AP5 prevented the AP5-mediated decrease in F-n but not the dose-dependent reduction in the CO2 bolus response. 7. Taken together, these data strongly suggest that the car otid chemoreceptor-mediated excitation of expiratory bulbospinal neuro nes is dependent on NMDA but not non-NMDA glutamate receptors.