title: Recruitment of excitatory serotonergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus post hypoxia and hypercapnia.
abstract: Inhibitory GABAergic and glycinergic neurotransmission to cardioinhibitory cardiac vagal neurons (CVNs) increase during inspiratory activity and likely mediate respiratory sinus arrhythmia, while the frequency of excitatory postsynaptic currents (EPSCs) in CVNs are unaltered during the different phases of respiration. However, following hypoxia and hypercapnia (H/H), the parasympathetic activity to the heart increases and thus far, identification of the pathways and neurotransmitters that are responsible for exciting CVNs post H/H are unclear. This study identifies different excitatory pathways to CVNs recruited post H/H. Spontaneous and inspiratory-related EPSCs were recorded in CVNs before, during, and after 10 min of H/H in an in vitro slice preparation that retains rhythmic respiratory activity. Before and during H/H, EPSCs in CVNs were completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5), selective AMPA/kainate and N-methyl-d-apartate (NMDA) receptor blockers, respectively. However, after H/H, there was a significant increase in EPSCs during each inspiratory burst. While some of the inspiratory-related EPSCs were blocked by the broad purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) and the specific P2X receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate monolithium trisodium salt (TNP-ATP) a P2X receptor blocker, most of the recruited excitatory neurotransmission to CVNs is serotonergic because odansetron, a selective 5-HT3 antagonist, abolished the majority of the spontaneous and inspiratory-related EPSCs evoked during recovery from H/H. The results from this study suggest that following episodes of H/H, two nonglutamatergic excitatory pathways, purinergic and serotonergic, activating P2X and 5-HT3 receptors, respectively, are recruited to excite CVNs in the post H/H recovery period.
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, 2300 Eye St. NW, Washington, DC 20037, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Kamendi
authors.forename: Q
authors.initials: Q
authors.lastname: Cheng
authors.forename: O
authors.initials: O
authors.lastname: Dergacheva
authors.forename: J G
authors.initials: JG
authors.lastname: Frank
authors.forename: C
authors.initials: C
authors.lastname: Gorini
authors.forename: H S
authors.initials: HS
authors.lastname: Jameson
authors.forename: R A
authors.initials: RA
authors.lastname: Pinol
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006935:Hypercapnia / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009714:Nucleus Accumbens / Q000473:pathology*; D017294:Ondansetron / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D012701:Serotonin; D017294:Ondansetron; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D000255:Adenosine Triphosphate; D014633:Valine