Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure.
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.
Idaho State University, Department of Biological Sciences and Dental Sciences, 921 S. 8th Avenue, Stop 8007, Pocatello, Idaho 83209, USA. pilajaso@isu.edu
Jason Q
JQ
Pilarski
Hilary E
HE
Wakefield
Andrew J
AJ
Fuglevand
Richard B
RB
Levine
Ralph F
RF
Fregosi
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine