title: Purinergic P2X receptors facilitate inhibitory GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
abstract: This study examined whether adenosine 5'-triphosphate (ATP) modulated inhibitory glycinergic and GABAergic neurotransmission to cardiac vagal neurons. Inhibitory 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 glycinergic and GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in cardiac vagal neurons which were blocked by the broad P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (100 microM). Application of the P2Y agonists uridine triphosphate (15 microM) and adenosine 5'-0-(Z-thiodiphosphate) (60 microM) did not enhance inhibitory neurotransmission to cardiac vagal neurons however, application of the selective P2X; receptor agonist, alpha, beta-methylene ATP (100 microM), increased glycinergic and GABAergic mIPSC neurotransmission to cardiac vagal neurons. The increase in inhibitory neurotransmission evoked by alpha, beta-methylene ATP was abolished by the selective P2X receptor antagonist 2',3'-O-(2,4,6-Trinitrophenyl) adenosine 5'-triphosphate (100 microM) indicating P2X receptors enhance the release of inhibitory neurotransmitters to cardiac neurons. The voltage-gated calcium channel blocker cadmium chloride did not alter the evoked increase in inhibitory mIPSCs. This work demonstrates that P2X receptor activation enhances inhibitory neurotransmission to parasympathetic cardiac vagal neurons and demonstrates an important functional role for ATP mediated purinergic signaling to cardiac vagal neurons.
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: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D005998:Glycine