title: Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus.
abstract: Motoneurons of the compact division of the nucleus ambiguus (cNA) are the final output neurons of the swallowing pattern generator. Thus, their normal function is critical to neonatal survival. To explore the role of purinergic signaling in modulating the excitability of these motoneurons during development, immunohistochemical and whole-cell recording techniques were used to characterize expression patterns of ionotropic P2X receptors and the effects of ATP on cNA motoneurons. Medullary slices containing the cNA were prepared from neonatal (P0-4) and juvenile (P15-21) rats. In neonatal cNA motoneurons, local application of 1 mM ATP produced a large (-133 +/- 17 pA; n = 78), desensitizing, inward current that was mimicked by 1 mM alpha,beta meATP and 2meSATP, and inhibited by the P2 antagonist, PPADS (5 microM), and the P2X3 antagonist, A-317481 (0.1-1 mM). In juvenile cNA motoneurons, 1 mM ATP produced negligible currents, while 10 mM ATP produced small (-59 +/- 14 pA; n = 42), primarily non-desensitizing currents. Immunohistochemistry demonstrated that in the neonate, the expression of P2X3 was robust, P2X2 and P2X5 moderate, P2X4 and P2X6 weak, and P2X1 absent. In the juvenile cNA, only low levels of P2X5 and P2X6 labeling were detected. These data indicate that P2X receptors in cNA motoneurons are profoundly downregulated during the first two postnatal weeks, and suggest a role for the purinoceptor system, particularly P2X3 receptors, in the control of esophageal motor networks during early postnatal periods.
authors.affiliation: Department of Physiology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Brosenitsch
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Adachi
authors.forename: Janusz
authors.initials: J
authors.lastname: Lipski
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Funk
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009714:Nucleus Accumbens / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010636:Phenols / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: C470346:A-317491; D004791:Enzyme Inhibitors; D010636:Phenols; D011083:Polycyclic Compounds; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C022571:adenosine 5'-O-(3-thiotriphosphate); D018698:Glutamic Acid; D013779:Tetrodotoxin; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate