Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus

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 mu M), and the P2X(3) 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 P2X(3) was robust, P2X(2) and P2X(5) moderate, P2X(4) and P2X(6) weak, and P2X(1) absent. In the juvenile cNA, only low levels of P2X(5) and P2X(6) 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 P2X(3) receptors, in the control of esophageal motor networks during early postnatal periods.