title: Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and after hypoxia and hypercapnia with prenatal nicotine exposure.
abstract: Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related excitatory inputs under normal conditions. However, excitatory purinergic and serotonergic pathways are recruited during inspiratory activity after episodes of hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to dramatically change cardiorespiratory responses and decrease the ability to resuscitate from H/H. This study tested whether PNN exposure alters excitatory neurotransmission to CVNs in the nucleus ambiguus during and after H/H. Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded in CVNs from rats that were exposed to nicotine (6 mg x kg(-1) x d(-1)) throughout the prenatal period. In contrast to unexposed animals, in PNN animals H/H recruited excitatory neurotransmission to CVNs during inspiratory-related activity that was blocked by the alpha3beta4 nicotinic acetylcholine receptor (nAChR) blocker alpha-conotoxin AuIB (alpha-CTX AuIB, 100 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 microM) and d(-)-2-amino-5-phosphonopentanoic acid (AP5, 50 microM), selective AMPA/kainate and N-methyl-d-aspartate receptor blockers, respectively. Following H/H, there was a significant increase in inspiratory-related excitatory postsynaptic currents that were unaltered by alpha-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (100 microM), a purinergic receptor blocker and CNQX and AP5. The results from this study demonstrate that with PNN exposure, an excitatory neurotransmission to CVNs is recruited during H/H that is glutamatergic and dependent on activation of alpha3beta4-containing nAChRs. Furthermore, exposure to PNN abolishes a serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced by recruitment of a glutamatergic pathway to CVNs post H/H.
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, 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: C
authors.initials: C
authors.lastname: Gorini
authors.forename: H S
authors.initials: HS
authors.lastname: Jameson
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
authors.forename: D
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D020916:Conotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D006321:Heart; D006935:Hypercapnia / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D020916:Conotoxins; D018683:Excitatory Amino Acid Agents; D018733:Nicotinic Antagonists; D012702:Serotonin Antagonists; C115558:conotoxin AuIB; D012701:Serotonin; D017294:Ondansetron; D009538:Nicotine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine