Pontine GABAergic pathways: role and plasticity in the hypoxic ventilatory response.
The hypoxic ventilatory response (HVR) was compared before and after uni- and bi-lateral injections of bicuculline, a GABA(A) receptor antagonist, into the ventrolateral (vl) pons and before and after conditioning animals to chronic sustained hypoxia (CSH). The HVR was assessed by recording phrenic nerve activity (PNA) during and after brief exposures to hypoxia (8% O(2) and 92% N(2) for 45s). Inspiratory (T(I)) and expiratory (T(E)) durations were averaged before hypoxia, at the peak breathing frequency during hypoxia, before the end of hypoxia, immediately after hypoxia, and 60s after hypoxia. Blocking GABA(A) receptors in the vl pons prolonged T(E) during, but not after hypoxia. After CSH induced by 14 days in a hypobaric chamber (0.5atm), the HVR was attenuated compared to that in the naive animals. This plasticity of HVR was associated with selective induction of alpha6 and delta GABA(A) receptor subunit mRNAs specifically in the pons compared to the medulla. These physiological and molecular results illustrate the importance of pontine GABAergic pathways in shaping the response to hypoxia.
Hsieh
Yee-Hsee
YH
Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4965, USA.
Siegel
Ruth E
RE
Dick
Thomas E
TE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D018496:Hyperoxia / Q000503:physiopathology*; D001239:Inhalation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008845:Microinjections / Q000379:methods; D016571:Neural Networks, Computer; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000503:physiopathology; D011149:Pons / Q000187:drug effects / Q000473:pathology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D012119:Respiration; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D021122:Protein Subunits; D012333:RNA, Messenger; D018079:Receptors, GABA; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline