Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and after hypoxia and hypercapnia with prenatal nicotine exposure
Journal of Neurophysiology
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. Copyright © 2009 The American Physiological Society.
Kamendi, H., Cheng, Q., Dergacheva, O., Gorini, C., Jameson, H., Wang, X., McIntosh, J., & Mendelowitz, D. (2009). Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and after hypoxia and hypercapnia with prenatal nicotine exposure. Journal of Neurophysiology, 101 (3). http://dx.doi.org/10.1152/jn.90680.2008