title: 5-HT2 receptors modulate excitatory neurotransmission to cardiac vagal neurons within the nucleus ambiguus evoked during and after hypoxia.
abstract: To examine the role of 5-HT2 receptors in the central cardiorespiratory network, and in particular the respiratory modulation of parasympathetic activity to the heart, we used an in vitro medullary slice that allowed simultaneous examination of rhythmic inspiratory-related activity recorded from hypoglossal rootlet and excitatory inspiratory-related neurotransmission to cardioinhibitory vagal neurons (CVNs) within the nucleus ambiguus (NA). Focal application of ketanserin, a 5-HT2 receptor antagonist, did not significantly alter the frequency of spontaneous excitatory postsynaptic excitatory currents (EPSCs) in CVNs in control conditions. However, ketanserin diminished spontaneous excitatory neurotransmission to CVNs during hypoxia. The inhibitory action of ketanserin was on 5-HT3 mediated EPSCs during hypoxia since these responses were blocked by the 5-HT3 receptor antagonist ondansetron. In addition, a robust inspiratory-related excitatory neurotransmission was recruited during recovery from hypoxia. Focal application of ketanserin during this posthypoxia period evoked a significant augmentation of the frequency of inspiratory-related, but not spontaneous EPSCs in CVNs. This excitatory effect of ketanserin was prevented by application of the purinergic receptor blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). These results demonstrate 5-HT2 receptors differentially modulate excitatory neurotransmission to CVNs during and after hypoxia. Activation of 5-HT2 receptors acts to maintain excitatory neurotransmission to CVNs during hypoxia, likely via presynaptic facilitation of 5-HT3 receptor-mediated neurotransmission to CVNs. However, activation of 5HT2 receptors diminishes the subsequent inspiratory-related excitatory neurotransmission to CVNs that is recruited during the recovery from hypoxia likely exerting an inhibitory action on inspiratory-related purinergic signaling.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC 20037, USA. olgad@gwu.edu
authors.forename: O
authors.initials: O
authors.lastname: Dergacheva
authors.forename: H
authors.initials: H
authors.lastname: Kamendi
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: R A
authors.initials: RA
authors.lastname: Pinol
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: C
authors.initials: C
authors.lastname: Gorini
authors.forename: H
authors.initials: H
authors.lastname: Jameson
authors.forename: M R
authors.initials: MR
authors.lastname: Lovett-Barr
authors.forename: D
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000294:innervation* / Q000502:physiology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017294:Ondansetron / Q000494:pharmacology; D009924:Organ Culture Techniques; D058914:Purinergic Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism*
chemical_list: D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D012701:Serotonin; D017294:Ondansetron; D011732:Pyridoxal Phosphate; D007650:Ketanserin