title: Genesis of gasping is independent of levels of serotonin in the Pet-1 knockout mouse.
abstract: Eupnea is normal breathing. If eupnea fails, as in severe hypoxia or ischemia, gasping is recruited. Gasping can serve as a powerful mechanism for autoresuscitation. A failure of autoresuscitation has been proposed as a basis of the sudden infant death syndrome. In an in vitro preparation, endogenous serotonin is reported to be essential for expression of gasping. Using an in situ preparation of the Pet-1 knockout mouse, we evaluated such a critical role for serotonin. In this mouse, the number of serotonergic neurons is reduced by 85-90% compared with animals without this homozygous genetic defect. Despite this reduction in the number of serotonergic neurons, phrenic discharge in eupnea and gasping of Pet-1 knockout mice was not different from that of wild-type mice. Indeed, gasping continued unabated, even after administration of methysergide, a blocker of many types of receptors for serotonin, to Pet-1 knockout mice. We conclude that serotonin is not critical for expression of gasping. The proposal for such a critical role, on the basis of observations in the in vitro slice preparation, may reflect the minimal functional neuronal tissue and neurotransmitters in this preparation, such that the role of any remaining neurotransmitters is magnified. Also, rhythmic activity of the in vitro slice preparation has been characterized as eupnea or gasping solely on the basis of activity of the hypoglossal nerve or massed neuronal activities of the ventrolateral medulla. The accuracy of this method of classification has not been established.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. walter.m.stjohn@dartmouth.edu
authors.forename: Walter M
authors.initials: WM
authors.lastname: St-John
authors.forename: Aihua
authors.initials: A
authors.lastname: Li
authors.forename: J C
authors.initials: JC
authors.lastname: Leiter
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004594:Electrophysiology; D005838:Genotype; D000860:Hypoxia / Q000503:physiopathology; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010791:Phrenic Nerve / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D012702:Serotonin Antagonists; D012701:Serotonin; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C495989:Pex1 protein, mouse; D008784:Methysergide