Autonomic innervation of airway smooth muscle

In several organs of the body, the parasympathetic innervation of smooth muscle is dual: excitatory (cholinergic) and inhibitory (Non-Adrenergic, Non-Cholinergic, or NANC). NANC nerves were a bit of a mystery for many years, as their name implies: they were defined by what they are not. Throughout the 1970's and 1980's we didn’t know what the transmitter released actually was, and there were lots of contenders. The general consensus now is that airway NANC nerves release mainly the gas NO, but might also co-release Vasoactive Intestinal Polypeptide (VIP) as well at higher frequencies of firing. This caused some kerfuffle because the general belief around this time was that individual nerves only released one neurotransmitter. Now we know that such co-transmission is relatively commonplace. What is also now clear is that cholinergic and NANC nerve terminals in airway smooth muscle arise from quite separate and distinct post-ganglionic neurons, which receive separate preganglionic innervation from the CNS.

airway autonomic innervation

Figure 1: Autonomic (parasympathetic) innervation of the airways. Contrary to what some textbooks will tell you, there is no sympathetic innervation of airway smooth muscle. The parasympathetic innervation of airway smooth muscle consists of cholinergic excitatory nerve fibres (releasing acetylcholine (ACh)) and so-called NANC inhibitory fibres (releasing mainly NO). The function of the NANC innervation in (patho)physiology is uncertain. The mucus-secreting glands of the airways also receive a cholinergic innervation. Muscarinic receptors on glands an smooth muscle mediate the effects of ACh in the airways.

The story isn’t terribly clear in the airways, where the function of the autonomic innervation isn’t obvious anyway. The cholinergic innervation makes some sort of sense: when you cough; bronchoconstriction helps stiffen the airways and narrows them allowing sheer forces to act better to dislodge mucus (the production of which is under cholinergic control). We know that the cholinergic innervation is activated in this very circumstance, and it may be that persistent cholinergic bronchospasm is due to inflammatory processes making sensory nerves hypersensitive. The function of the opposing NANC innervation presumably acts as some sort of brake, or may just be an evolutionary or embryological vestige (a bit like your appendix).

The story is much clearer in the stomach where relaxation and contraction serve obvious physiological functions. The parasympathetic innervation is similar to that of the airways, consisting of a mixture of excitatory cholinergic and inhibitory NANC (NO, and maybe VIP and even other transmitters) nerves. During receptive relaxation to accommodate a meal, the NANC nerves are brought into play. When the stomach contracts to empty its contents into the duodenum the cholinergic innervation is activated. Maybe the innervation of the airways simply mirrors the common embryological origin of both organs? Nobody really knows.

Listed in Cases