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 α4* 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 α4* 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. |
