Abolishment of Serotonergic Neurotransmission to Cardiac Vagal Neurons During and After Hypoxia and Hypercapnia With Prenatal Nicotine Exposure
| Autor: | Q. Cheng, Xin Wang, David Mendelowitz, Christopher Gorini, Olga Dergacheva, Heather Jameson, J. M. McIntosh, Harriet Kamendi |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Nicotine Serotonin Physiology Excitatory Amino Acid Agents Action Potentials Nicotinic Antagonists In Vitro Techniques Neurotransmission Serotonergic Synaptic Transmission Hypercapnia Pregnancy Animals Medicine Drug Interactions Hypoxia 6-Cyano-7-nitroquinoxaline-2 3-dione Neurons Dose-Response Relationship Drug business.industry General Neuroscience Purinergic receptor Heart Vagus Nerve Valine Articles Ondansetron Rats Vagus nerve Animals Newborn Prenatal Exposure Delayed Effects Excitatory postsynaptic potential Female Serotonin Antagonists Conotoxins business Neuroscience medicine.drug |
| Zdroj: | Journal of Neurophysiology. 101:1141-1150 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.90680.2008 |
| Popis: | 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·kg−1·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 α3β4 nicotinic acetylcholine receptor (nAChR) blocker α-conotoxin AuIB (α-CTX AuIB, 100 μM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 μM) and d(−)-2-amino-5-phosphonopentanoic acid (AP5, 50 μM), 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 α-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2′, 4′-disulphonic acid (100 μM), 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 α3β4-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. |
| Databáze: | OpenAIRE |
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