Key result
Following hypoxia and hypercapnia, purinergic and serotonergic pathways are recruited to excite cardiac vagal neurons via P2X and 5-HT3 receptors, respectively.
This study identifies that purinergic and serotonergic pathways are recruited to excite cardiac vagal neurons following hypoxia and hypercapnia, providing insight into parasympathetic control of the heart post-H/H.
Advances understanding of vagal excitation during respiratory stress in animals; leaves open human translation and clinical relevance.
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.
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Kamendi et al. (2008) studied Hypoxia and hypercapnia effects on cardiac vagal neurons. Hypoxia and hypercapnia (H/H) and receptor antagonists vs. Before and during H/H was evaluated on Spontaneous and inspiratory-related excitatory postsynaptic currents (EPSCs). Following hypoxia and hypercapnia, purinergic and serotonergic pathways are recruited to excite cardiac vagal neurons via P2X and 5-HT3 receptors, respectively.
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