Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA recept
June 29th, 2008 | by admin |Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats.
NMDA receptor antagonism in the phrenic motonucleus area eliminates phrenic long-term facilitation (pLTF, a persistent augmentation of phrenic nerve activitiy after episodic hypoxia) in anesthetized rats. However, whether NMDA antagonism can eliminate ventilatory LTF (vLTF) in awake rats is unclear. The role of non-NMDA receptors in LTF is also unknown. It has been reported that serotonin receptor antagonism before, but not after, episodic hypoxia eliminates pLTF, suggesting that serotonin receptors are required for induction, but not maintenance, of pLTF. However, since NMDA and non-NMDA ionotropic glutamate receptors are directly involved in mediating the inspiratory drive to phrenic, hypoglossal and intercostal motoneurons, we hypothesized that these receptors are required for both formation and maintenance of vLTF. vLTF, induced by 5 episodes of 5-min poikilocapnic hypoxia (10% O2) with 5-min normoxia intervals, was measured with plethysmography in conscious adult male Sprague-Dawley rats. Either APV (NMDA antagonist, 1.5 mg/kg) or CNQX (non-NMDA antagonist, 10 mg/kg) was systemically (i.p.) injected ~30 min before hypoxia. APV was also injected immediately after or 20 min after episodic hypoxia in additional groups. As control, vehicle was similarly injected in each rat 1-2 days before. Regardless of being injected before or after episodic hypoxia, vehicle did not alter vLTF (~23%), whereas APV eliminated vLTF while having little effect on baseline ventilation or hypoxic ventilatory response. In contrast, CNQX enhanced vLTF (~34%) while decreasing baseline ventilation. Collectively, these results suggest that activation of NMDA but not non-NMDA receptors is necessary for formation and maintenance of vLTF in awake rats. Key words: Respiratory Control, Plasticity, Intermittent hypoxia, APV, CNQX.
McGuire M, Liu C, Cao Y, Ling L.
Division of Sleep Medicine, Brigham and Women\’s Hospital, Boston, Massachusetts, United States; Boston, Massachusetts, United States.