title: Noradrenergic modulation of XII motoneuron inspiratory activity does not involve alpha2-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 alpha2-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 alpha2-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 approximately 40%, but an Ih current blocker (ZD7288), at concentrations that blocked approximately 80% of Ih, had no effect on inspiratory burst amplitude. The clonidine inhibition was unaffected by the GABAA antagonist (+)bicuculline but attenuated by the alpha2-antagonist rauwolscine and the imidazoline 1 (I1) antagonist efaroxan. The I1 agonist rilmenidine, but not the alpha2-agonist UK14304, inhibited XII output. Clonidine also reduced action potential amplitude or impaired repetitive firing. Although a contribution from alpha2, and in particular I1, receptors remains possible, results demonstrate that 1) noradrenergic modulation of XII inspiratory activity is unlikely to involve alpha2-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.
authors.affiliation: 7-50 Medical Sciences Bldg., Dept. of Physiology, Univ. of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Adachi
authors.forename: Dean M
authors.initials: DM
authors.lastname: Robinson
authors.forename: Gareth B
authors.initials: GB
authors.lastname: Miles
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Funk
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D001239:Inhalation / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018341:Receptors, Adrenergic, alpha-2; D018698:Glutamic Acid; D003000:Clonidine; D009638:Norepinephrine