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First published online August 17, 2007
Journal of Experimental Biology 210, 3015-3026 (2007)
Published by The Company of Biologists 2007
doi: 10.1242/jeb.005983

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Developmental changes in central O₂ chemoreflex in Rana catesbeiana: the role of noradrenergic modulation

Stéphanie Fournier, Mathieu Allard, Stéphanie Roussin and Richard Kinkead^*

Department of Pediatrics, Université Laval, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, QC, Canada

^* Author for correspondence (e-mail: Richard.Kinkead{at}crsfa.ulaval.ca)

Accepted 18 June 2007

The in vitro brainstem preparation from Rana catesbeiana shows a functional central O₂ chemoreflex. Acute brainstem exposure to hypoxic superfusate elicits lung burst frequency responses that change over the course of development. Based on studies suggesting that brainstem noradrenergic neurons are involved in this reflex, we tested the following two hypotheses in vitro: (1) activation of adrenoceptors is necessary for the expression of the fictive lung ventilation response to hypoxia, and (2) changes in fast, Cl^–-dependent neurotransmission (GABA/glycine) contribute to developmental changes in noradrenergic modulation. Experiments were performed on preparations from pre-metamorphics tadpoles (TK stages V–XIII) and adult bullfrogs. Acute exposure to hypoxic superfusate (98% N₂, 2% CO₂) increased fictive lung ventilation frequency in the pre-metamorphic group, whereas a decrease was observed in adults. Buccal burst frequency was unchanged by hypoxia. Noradrenaline (NA; 5 µmol l^–1) bath application mimicked both fictive breathing responses and application of the ₁-antagonist prazosine (0.5 µmol l^–1) blocked the lung burst response to hypoxia in both groups. Blocking GABA_A/glycine receptors with a bicuculine/strychnine mixture (1.25 µmol l^–1/1.5 µmol l^–1, respectively) or activation of GABA_B pre-synaptic autoreceptors with baclofen (0.5 µmol l^–1) prevented the lung burst response to hypoxia and to the ₁-agonist phenylephrine (25 µmol l^–1) in both stage groups. We conclude that NA modulation contributes to the central O₂ chemoreflex in bullfrog, which acts via GABA/glycine pathways. These data suggest that maturation of GABA/glycine neurotransmission contributes to the developmental changes in this chemoreflex.

Key words: control of breathing, amphibian, GABA, chloride, bicarbonate

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