Noradrenergic modulation of XII motoneuron inspiratory activity does not involve α2-receptor inhibition of the Ih current or presynaptic glutamate release

Abstract

Norepinephrine has powerful and diverse modulatory effects on hypoglossal (XII) motoneuron activity, which is important in maintaining airway patency. The objective was to test two hypotheses that α2-adrenoceptor-mediated, presynaptic inhibition of glutamatergic inspiratory drive (Selvaratnam SR, Parkis MA, and Funk GD. Brain Res 805: 104–115, 1998) and postsynaptic inhibition of the hyperpolarization-activated inward current ( Ih) (Parkis MA and Berger AJ. Brain Res 769: 108–118, 1997) modulate XII inspiratory activity. Nerve and whole cell recordings were applied to rhythmic medullary slice preparations from neonatal rats ( postnatal days 0–4) to monitor XII inspiratory burst amplitude and motoneuron properties. Application of an α2-receptor agonist (clonidine, 1 mM) to the XII nucleus reduced inspiratory burst amplitude to 71 ± 3% of control but had no effect on inspiratory synaptic currents. It also reduced the Ih current by ∼40%, but an Ih current blocker (ZD7288), at concentrations that blocked ∼80% of Ih, had no effect on inspiratory burst amplitude. The clonidine inhibition was unaffected by the GABAA antagonist (+)bicuculline but attenuated by the α2-antagonist rauwolscine and the imidazoline 1 (I1) antagonist efaroxan. The I1 agonist rilmenidine, but not the α2-agonist UK14304, inhibited XII output. Clonidine also reduced action potential amplitude or impaired repetitive firing. Although a contribution from α2, and in particular I1, receptors remains possible, results demonstrate that 1) noradrenergic modulation of XII inspiratory activity is unlikely to involve α2-receptor-mediated presynaptic inhibition of glutamate release or modulation of Ih; 2) inhibition of repetitive firing is a major factor underlying the inhibition of XII output by clonidine; and 3) Ih is present in neonatal XII motoneurons but does not contribute to shaping their inspiratory activity.