Purinergic P2X receptors mediate excitatory transmission to cardiac vagal neurons in the nucleus ambiguus after hypoxia.
Challenges such as hypoxia elicit a powerful response from both the central cardiovascular and respiratory neuronal networks. Recent work indicates that purinergic neurotransmission in the brain stem is an important modulator of central respiratory network responses to hypoxia. This study tests whether alterations in purinergic neurotransmission extend beyond respiratory responses to hypoxia and also mediates respiratory inputs to cardiac vagal neurons. To examine central cardiorespiratory responses to hypoxia, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and synaptic neurotransmission to cardioinhibitory vagal neurons. Here we show that P2X receptor activation mediates respiratory-related excitatory neurotransmission to parasympathetic cardiac vagal neurons, the dominant control of heart rate. These data demonstrate a critical functional role for adenosine 5'-triphosphate-mediated purinergic signaling in facilitating respiratory-related excitatory neurotransmission to cardiac vagal neurons after hypoxia.
Griffioen
Kathleen J
KJ
Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037, USA.
Gorini
Christopher
C
Jameson
Heather
H
Mendelowitz
David
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons; D010275:Parasympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013113:Spin Labels; D009435:Synaptic Transmission; D014630:Vagus Nerve / Q000473:pathology / Q000503:physiopathology*
D000975:Antioxidants; D003497:Cyclic N-Oxides; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D013113:Spin Labels; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; C001803:tempol