title: Adrenergic α₁ receptor activation is sufficient, but not necessary for phrenic long-term facilitation.
abstract: Acute intermittent hypoxia (AIH; three 5-min hypoxic episodes) causes a form of phrenic motor facilitation (pMF) known as phrenic long-term facilitation (pLTF); pLTF is initiated by spinal activation of Gq protein-coupled 5-HT2 receptors. Because α1 adrenergic receptors are expressed in the phrenic motor nucleus and are also Gq protein-coupled, we hypothesized that α1 receptors are sufficient, but not necessary for AIH-induced pLTF. In anesthetized, paralyzed, and ventilated rats, episodic spinal application of the α1 receptor agonist phenylephrine (PE) elicited dose-dependent pMF (10 and 100 μM, P < 0.05; but not 1 μM). PE-induced pMF was blocked by the α1 receptor antagonist prazosin (1 mM; -20 ± 20% at 60 min, -5 ± 21% at 90 min; n = 6). Although α1 receptor activation is sufficient to induce pMF, it was not necessary for AIH-induced pLTF because intrathecal prazosin (1 mM) did not alter AIH-induced pLTF (56 ± 9% at 60 min, 78 ± 12% at 90 min; n = 9). Intravenous (iv) prazosin (150 μg/kg) appeared to reduce pLTF (21 ± 9% at 60 min, 26 ± 8% at 90 min), but this effect was not significant. Hypoglossal long-term facilitation was unaffected by intrathecal prazosin, but was blocked by iv prazosin (-4 ± 14% at 60 min, -13 ± 18% at 90 min), suggesting different LTF mechanisms in different motor neuron pools. In conclusion, Gq protein-coupled α1 adrenergic receptors evoke pMF, but they are not necessary for AIH-induced pLTF.
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors: A G
authors: AG
authors: Huxtable
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors: P M
authors: PM
authors: MacFarlane
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors: S
authors: S
authors: Vinit
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors: N L
authors: NL
authors: Nichols
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors: E A
authors: EA
authors: Dale
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin mitchell@svm.vetmed.wisc.edu.
authors: G S
authors: GS
authors: Mitchell
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage*; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D066193:Cervical Cord / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1
keywords: plasticity; respiratory motor neuron; spinal cord; α1 receptors