title: Episodic stimulation of alpha1-adrenoreceptors induces protein kinase C-dependent persistent changes in motoneuronal excitability.
abstract: In vitro long-term facilitation (ivLTF) is a novel form of activity-independent postsynaptic enhancement of AMPA receptor function in hypoglossal (XII) motoneurons that can be induced by intermittent activation of 5-HT2 receptors. In vivo respiratory long-term facilitation (LTF) is characterized by a persistent 5-HT2 receptor-dependent increase in respiratory motor output or ventilation after episodic exposures to hypoxia in adult rats. Here, we demonstrate that ivLTF can also be induced by episodic but not continuous stimulation of alpha1-adrenergic receptors that requires protein kinase C (PKC), but not PKA (protein kinase A), activation. Additionally, we show that in vivo respiratory LTF is also alpha1-adrenergic receptor dependent. We suggest that, in vivo, concurrent episodic activation of 5-HT2 and alpha1-adrenergic receptors is necessary to produce long-lasting changes in the excitability of respiratory motoneurons, possibly involving PKC activation via the G alpha(q)-PLC (phospholipase C) signaling pathway common to both receptor subtypes. Such plasticity of XII motor output may increase upper airway muscle (innervated by XII nerve) tone and improve the likelihood that airway patency will be maintained. Elucidating the mechanism underlying LTF can be of clinical importance to the patients suffering from sleep-disordered breathing.
authors: Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095-1763, USA.
authors: Natalia V
authors: NV
authors: Neverova
authors: Shane A
authors: SA
authors: Saywell
authors: Lisa J
authors: LJ
authors: Nashold
authors: Gordon S
authors: GS
authors: Mitchell
authors: Jack L
authors: JL
authors: Feldman
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D007002:Hypoglossal Nerve / Q000502:physiology*; D008526:Medulla Oblongata / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology; D012701:Serotonin / Q000378:metabolism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D012701:Serotonin; D011493:Protein Kinase C; D011224:Prazosin