P2 RECEPTOR EXCITATION OF RODENT HYPOGLOSSAL MOTONEURON ACTIVITY IN-VITRO AND IN-VIVO - A MOLECULAR PHYSIOLOGICAL ANALYSIS

The role of P2 receptors in controlling hypoglossal motoneuron (XII MN ) output was examined (1) electrophysiologically, via application of A TP to the hypoglossal nucleus of rhythmically active mouse medullary s lices and anesthetized adult rats; (2) immunohistochemically, using an antiserum against the P2X(2) receptor subunit; and (3) using PCR to i dentify expression of P2X(2) receptor subunits in micropunches of tiss ue taken from the XII motor nucleus. Application of ATP to the hypoglo ssal nucleus of mouse medullary slices and anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve activity. Addition al in vitro effects included potentiation of inspiratory hypoglossal n erve output via a suramin-and pyridoxal-phosphate-6-azophenyl-2',4'-di sulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via activation of a suramin-sensitive inward current, decreased neuronal i nput resistance, and a slow-onset theophylline-sensitive reduction of inspiratory output likely resulting from hydrolysis of extracellular A TP to adenosine and activation of P1 receptors. Immunohistoctlemically , P2X(2) receptors were detected in inspiratory XII MNs that were labe led with Lucifer yellow. These data, combined with identification of m RNA for three P2X(2) receptor subunit isoforms within the hypoglossal nucleus (two of which have not been localized previously in brain) and the previous demonstration that P2X receptors are ubiquitously expres sed in cranial and spinal motoneuron pools, support not only a role of P2 receptors in modulating inspiratory hypoglossal activity but a gen eral role of P2 receptors in modulating motor outflow from the CNS.