DEVELOPMENTAL MODULATION OF MOUSE HYPOGLOSSAL NERVE INSPIRATORY OUTPUT IN-VITRO BY NORADRENERGIC RECEPTOR AGONISTS

The ontogeny of the noradrenergic receptor subtypes modulating hypoglo ssal (XII) nerve inspiratory output was characterized. Noradrenergic a gents were locally applied over the XII nucleus of rhythmically active medullary slice preparations isolated from mice between zero and 13 d ays of age (P0-P13) and the effects on XII inspiratory burst amplitude quantified. The alpha(1) receptor agonist phenylephrine (PE, 0.1-10 m u M) produced a dose-dependent, prazosin-sensitive (0.1-10 mu M) incre ase in XII nerve inspiratory burst amplitude. The magnitude of this po tentiation increased steadily from a maximum of 15 +/- 8% in P0 mice t o 134 +/- 4% in P12-P13 mice. The beta receptor agonist isoproterenol (0.01-1.0 mM) produced a prazosin-insensitive, propranolol-sensitive p otentiation of XII nerve burst amplitude. The isoproterenol-mediated p otentiation increased with development from 27 +/- 5% in P0-P1 slices, to 37 +/- 3% in P3 slices and 45 +/- 4% in P9-P10 slices. The alpha(2 ) receptor agonist clonidine (1 mM) reduced XII nerve inspiratory burs t amplitude in P0-P3 slices by 29 +/- 5%, but had no effect on output from P12-P13 slices. An alpha(2) receptor-mediated inhibition of inspi ratory activity in neonates (P0-P3) was further supported by a 19 +/- 3% reduction in XII nerve burst amplitude when norepinephrine (NE, 100 mu M) was applied in the presence of prazosin (10 mu M) and propanolo l (100 mu M) Results indicate that developmental increases in potentia ting alpha(1) and, to a lesser extent, beta receptor mechanisms combin e with a developmentally decreasing inhibitory mechanism, most likely mediated by alpha(2) receptors, to determine the ontogenetic time cour se by which NE modulates XII MN inspiratory activity. (C) 1998 Elsevie r Science B.V. All rights reserved.