Central cholinergic regulation of respiration: nicotinic receptors.
Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of alpha4* nAChRs in the preBötzinger Complex (preBötC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBötC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic alpha4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.
Shao
Xuesi M
XM
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1763, USA. mshao@ucla.edu
Feldman
Jack L
JL
D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology; D011247:Pregnancy; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012119:Respiration; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000188:drug therapy / Q000503:physiopathology; D013398:Sudden Infant Death / Q000209:etiology / Q000517:prevention & control
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D009538:Nicotine