Adrenergic α₁ receptor activation is sufficient, but not necessary for phrenic long-term facilitation

J Appl Physiol (1985). 2014 Jun 1;116(11):1345-52. doi: 10.1152/japplphysiol.00904.2013. Epub 2014 Feb 13.

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.

Keywords: plasticity; respiratory motor neuron; spinal cord; α1 receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / administration & dosage*
  • Adrenergic alpha-1 Receptor Antagonists / administration & dosage*
  • Animals
  • Cervical Cord / drug effects
  • Cervical Cord / physiopathology
  • Dose-Response Relationship, Drug
  • Hypoxia / metabolism*
  • Long-Term Potentiation / drug effects*
  • Male
  • Motor Neurons / drug effects*
  • Neuronal Plasticity / drug effects
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / metabolism*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Receptors, Adrenergic, alpha-1