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This Article Full Text Full Text (PDF) All Versions of this Article: 574/2/535    most recent jphysiol.2006.108829v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ren, J. Articles by Greer, J. J. Search for Related Content PubMed PubMed Citation Articles by Ren, J. Articles by Greer, J. J. Related Collections Respiratory

¹ Department of Physiology, Division of Neuroscience, 513 HMRC, University of Alberta, Edmonton Alberta, Canada T6G 2S2

Neurosteroids regulate neuronal excitability and are expressed at particularly high levels in the CNS during the perinatal period. Further, neurosteroid levels are increased by a variety of stressors including hypoxia, asphyxia, parturition, ethanol exposure and infection. One mechanism by which neurosteroids regulate neuronal activity is by negative or positive modulation of GABA_A receptor function. Perinatal respiration is strongly modulated by GABAergic synaptic drive, and GABA release is increased during hypoxia to contribute to hypoxia-induced depression of neonatal ventilation. Here, we use in vitro and in vivo rat models to test the hypothesis that GABA_A receptor-mediated modulation of perinatal respiration is markedly influenced by the presence of neurosteroids. The principal finding of this study was that the efficacy of GABA_A receptor-mediated modulation of respiratory membrane potential and rhythmogenesis is markedly enhanced by allopregnanolone and depressed by dehydroepiandrosterone sulphate. These data demonstrate that the modulation of breathing via GABA_A receptor activation will be determined by the overall balance of negative and positive neurosteroid modulators within respiratory nuclei. This adds a level of complexity that must be considered when examining the depression of breathing in mammals associated with various behavioural states and pathogenic conditions such as apnoea and sudden death suspected to be associated with central respiratory dysfunction.

(Received 2 March 2006; accepted after revision 6 May 2006; first published online 11 May 2006)
Corresponding author J. J. Greer: University of Alberta, Department of Physiology, 513 HMRC, Edmonton, AB, Canada T6G 2S2. Email: john.greer{at}ualberta.ca

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