title: ATP facilitates glutamatergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
abstract: Recent work has shown that adenosine 5'-triphosphate (ATP) plays an important role in modulating the activity of parasympathetic cardiac vagal neurons that dominate the neural control of heart rate. This study examined the mechanisms by which activation of ATP receptors modulates excitatory neurotransmission to cardiac vagal neurons. Glutamatergic activity to cardiac vagal neurons was isolated and examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation in rats. ATP (100 microM) evoked increases in the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cardiac vagal neurons which were blocked by the broad P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 microM). Application of the selective P2X receptor agonist, alpha, beta-methylene ATP (100 microM), also increased glutamatergic mEPSCs neurotransmission to cardiac vagal neurons indicating P2X receptors enhance glutamatergic release to cardiac vagal neurons. The evoked increase in glutamatergic mEPSC was unaltered by the voltage-gated calcium channel blocker cadmium, and was abolished by the selective P2X receptor antagonist 2',3'-O-(2,4,6-Trinitrophenyl) adenosine 5'-triphosphate, TNP-ATP (100 microM). This work demonstrates that the ATP evoked facilitation of excitatory neurotransmission to cardiac vagal neurons is dependent upon activation of P2X receptors on glutamatergic presynaptic terminals.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC 20037, USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Jameson
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Pinol
authors.forename: Harriet
authors.initials: H
authors.lastname: Kamendi
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006321:Heart / Q000294:innervation; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate