Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure

Jason Q. Pilarski, Hilary E. Wakefield, Andrew J. Fuglevand, Richard B. Levine, Ralph F. Fregosi

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on hypoglossal motor neurons (XII MNs) that innervate muscles of the tongue. Activation of XII MN nAChRs evokes depolarizing currents, which are important for regulating the size and stiffness of the upper airway. Although data show that chronic developmental nicotine exposure (DNE) blunts cholinergic neurotransmission in the XII motor nucleus, it is unclear how nAChRs are involved. Therefore, XII MN nAChR desensitization and recovery were examined in tissues from DNE or control pups using a medullary slice preparation and tight-seal whole cell patch-clamp recordings. nAChR-mediated inward currents were evoked by brief pressure pulses of nicotine or the α4β2 nAChR agonist RJR-2403. We found that, regardless of treatment, activatable nAChRs underwent desensitization, but, following DNE, nAChRs exhibited increased desensitization and delayed recovery. Similar results were produced using RJR-2403, showing that DNE influences primarily the α4β2 nAChR subtype. These results show that while some nAChRs preserve their responsiveness to acute nicotine following DNE, they more readily desensitize and recover more slowly from the desensitized state. These data provide new evidence that chronic DNE modulates XII MN nAChR function, and suggests an explanation for the association between DNE and the incidence of central and obstructive apneas.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalJournal of neurophysiology
Volume107
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Obstructive sleep apnea
  • Tongue

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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