μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive

Erica S. Levitt, Ana P. Abdala, Julian F R Paton, John M. Bissonnette, John Williams

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Opioid-induced respiratory effects include aspiration and difficulty swallowing, suggesting impairment of the upper airways. The pontine Kölliker-Fuse nucleus (KF) controls upper airway patency and regulates respiration, in particular the inspiratory/expiratory phase transition. Given the importance of the KF in coordinating respiratory pattern, the mechanisms of μ opioid receptor activation in this nucleus were investigated at the systems and cellular level. In anaesthetized, vagi-intact rats, injection of opioid agonists DAMGO or [Met5]enkephalin (ME) into the KF reduced respiratory frequency and amplitude. The μ opioid agonist DAMGO applied directly into the KF of the in situ arterially perfused working heart-brainstem preparation of rat resulted in robust apneusis (lengthened low amplitude inspiration due to loss of post-inspiratory drive) that was rapidly reversed by the opioid antagonist naloxone. In brain slice preparations, activation of μ opioid receptors on KF neurons hyperpolarized a distinct population (61%) of neurons. As expected, the opioid-induced hyperpolarization reduced the excitability of the neuron in response to either current injection or local application of glutamate. In voltage-clamp recordings the outward current produced by the opioid agonist ME was concentration dependent, reversed at the potassium equilibrium potential and was blocked by BaCl2, characteristics of a G protein-coupled inwardly rectifying potassium (GIRK) conductance. The clinically used drug morphine produced an outward current in KF neurons with similar potency to morphine-mediated currents in locus coeruleus brain slice preparations. Thus, the population of KF neurons that are hyperpolarized by μ opioid agonists are likely mediators of the opioid-induced loss of post-inspiration and induction of apneusis.

Original languageEnglish (US)
Pages (from-to)4453-4469
Number of pages17
JournalJournal of Physiology
Volume593
Issue number19
DOIs
StatePublished - Oct 1 2015

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Opioid Receptors
Opioid Analgesics
Neurons
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Enkephalins
Morphine
Potassium
Injections
Airway Management
Locus Coeruleus
Narcotic Antagonists
Phase Transition
Brain
Deglutition
Naloxone
GTP-Binding Proteins
Population
Brain Stem
Glutamic Acid
Respiration

ASJC Scopus subject areas

  • Physiology

Cite this

μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive. / Levitt, Erica S.; Abdala, Ana P.; Paton, Julian F R; Bissonnette, John M.; Williams, John.

In: Journal of Physiology, Vol. 593, No. 19, 01.10.2015, p. 4453-4469.

Research output: Contribution to journalArticle

Levitt, Erica S. ; Abdala, Ana P. ; Paton, Julian F R ; Bissonnette, John M. ; Williams, John. / μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive. In: Journal of Physiology. 2015 ; Vol. 593, No. 19. pp. 4453-4469.
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