Phrenic long-term facilitation requires NMDA receptors in the phrenic motonucleus in rats.
Exposure to episodic hypoxia induces a persistent augmentation of respiratory activity, known as long-term facilitation (LTF). LTF of phrenic nerve activity has been reported to require serotonin receptor activation and protein syntheses. However, the underlying cellular mechanism still remains poorly understood. NMDA receptors play key roles in synaptic plasticity (e.g. some forms of hippocampal long-term potentiation). The present study was designed to examine the role of NMDA receptors in phrenic LTF and test if the relevant receptors are located in the phrenic motonucleus. Integrated phrenic nerve activity was measured in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats before, during and after three episodes of 5 min isocapnic hypoxia (P(a,O2) = 30-45 mmHg), separated by 5 min hyperoxia (50% O2). Either saline (as control) or the NMDA receptor antagonist MK-801 (0.2 mg kg(-1), i.p.) was systemically injected approximately 1 h before hypoxia. Phrenic LTF was eliminated by the MK-801 injection (vehicle, 32.8 +/- 3.7% above baseline in phrenic amplitude at 60 min post-hypoxia; MK-801, -0.5 +/- 4.1%, means +/- S.E.M.), with little change in both the CO2-apnoeic threshold and the hypoxic phrenic response (HPR). Vehicle (saline, 5 x 100 nl) or MK-801 (10 microM; 5 x 100 nl) was also microinjected into the phrenic motonucleus region in other groups. Phrenic LTF was eliminated by the MK-801 microinjection (vehicle, 34.2 +/- 3.4%; MK-801, -2.5 +/- 2.8%), with minimal change in HPR. Collectively, these results suggest that the activation of NMDA receptors in the phrenic motonucleus is required for the episodic hypoxia-induced phrenic LTF.
McGuire
Michelle
M
Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Zhang
Yi
Y
White
David P
DP
Ling
Liming
L
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate