title: Intermittent hypercapnia enhances CO₂ responsiveness and overcomes serotonergic dysfunction.
abstract: Serotonergic dysfunction compromises ventilatory chemosensitivity and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). We have shown raphé contributions to central chemosensitivity involving serotonin (5-HT)-and γ-aminobutyric acid (GABA)-mediated mechanisms. We tested the hypothesis that mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of GABA mechanisms. Rat pups were IHc-pretreated (eight consecutive cycles; 5 min 5% CO2 - air, 10 min air) or constant normocapnia-pretreated as a control, each day for 5 consecutive days beginning at P12. We subsequently assessed CO2 responsiveness using the in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. Results show IHc-pretreatment induces plasticity sufficient for responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. Responsiveness following IHc-pretreatment was absent if ketanserin was combined with GABAergic antagonism, indicating that plasticity depends on GABAergic mechanisms. We propose that IHc-induced plasticity could reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.
authors.affiliation: University of Alaska Fairbanks, Biology and Wildlife Department, Fairbanks, AK, United States.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Mosher
authors.affiliation: University of Alaska Fairbanks, Biology and Wildlife Department, Fairbanks, AK, United States; Institute of Arctic Biology, Fairbanks, AK, United States.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Taylor
authors.affiliation: University of Alaska Fairbanks, Biology and Wildlife Department, Fairbanks, AK, United States; Institute of Arctic Biology, Fairbanks, AK, United States. Electronic address: mbharris@alaska.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Harris
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism*; D005260:Female; D006935:Hypercapnia / Q000188:drug therapy / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D012702:Serotonin Antagonists; D002245:Carbon Dioxide; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D007650:Ketanserin
keywords: Chemosensitivity; GABA; Respiration; SIDS; Serotonin