Persistence of eupnea and gasping following blockade of both serotonin type 1 and 2 receptors in the in situ juvenile rat preparation.
In severe hypoxia or ischemia, normal eupneic breathing is replaced by gasping, which can serve as a powerful mechanism for "autoresuscitation." We have proposed that gasping is generated by medullary neurons having intrinsic pacemaker bursting properties dependent on a persistent sodium current. A number of neuromodulators, including serotonin, influence persistent sodium currents. Thus we hypothesized that endogenous serotonin is essential for gasping to be generated. To assess such a critical role for serotonin, a preparation of the perfused, juvenile in situ rat was used. Activities of the phrenic, hypoglossal, and vagal nerves were recorded. We added blockers of type 1 and/or type 2 classes of serotonergic receptors to the perfusate delivered to the preparation. Eupnea continued following additions of any of the blockers. Changes were limited to an increase in the frequency of phrenic bursts and a decline in peak heights of all neural activities. In ischemia, gasping was induced following any of the blockers. Few statistically significant changes in parameters of gasping were found. We thus did not find a differential suppression of gasping, compared with eupnea, following blockers of serotonin receptors. Such a differential suppression had been proposed based on findings using an in vitro preparation. We hypothesize that multiple neurotransmitters/neuromodulators influence medullary mechanisms underlying the neurogenesis of gasping. In greatly reduced in vitro preparations, the importance of any individual neuromodulator, such as serotonin, may be exaggerated compared with its role in more intact preparations.
Toppin
Veronica A L
VA
Institute of Arctic Biology, University of Alaska Fairbanks, Alaska, USA.
Harris
Michael B
MB
Kober
Anna M
AM
Leiter
J C
JC
St-John
Walter M
WM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003655:Decerebrate State; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology; D008168:Lung / Q000294:innervation*; D008784:Methysergide / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D044402:Receptor, Serotonin, 5-HT2A; D044263:Receptors, Serotonin, 5-HT1; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D008784:Methysergide