NEUROPHYSIOLOGY | Neural Control of Airway Smooth Muscle

Airway smooth muscle (ASM) is the primary effector cell responsible for controlling airway caliber and thus the resistance to airflow of the entire tracheobronchial tree. The autonomic nervous system is the principal regulator of the ASM tone and consists of three separate neural pathways. First, parasympathetic (vagal) innervation of ASM is the primary contractile pathway, and acetylcholine causes ASM contraction by activating the M 3 muscarinic cholinoceptors. Second, sympathetic innervation of human ASM is relatively sparse, but epinephrine secreted by adrenal medulla can induce ASM relaxation by activating the β 2 adrenoceptor. Third, the existence of nonadrenergic, noncholinergic (NANC) innervation of ASM has been demonstrated in various species including humans. The inhibitory NANC fibers are carried in parasympathetic nerves, and vasoactive intestinal peptide and nitric oxide are the putative neurotransmitters. The excitatory NANC mechanism involves the ‘efferent’ functions of vagal bronchopulmonary sensory nerves that release tachykinins upon activation and cause ASM contraction. Bronchoconstriction is an important component of the airway defense reflexes elicited by inhaled irritants. Three subtypes of vagal bronchopulmonary afferents function as the primary sensors of inhaled irritants: C-fiber afferents (tachykinin-containing afferents), rapidly adapting pulmonary receptors, and laryngeal afferents. Compelling evidence suggests that hypersensitivity of these airway afferents and autonomic nerve dysfunction and/or dysregulation are important contributing factors in the pathogenesis of airway hyperresponsiveness. A better understanding of the mechanisms underlying the neural control of ASM tone should help in the development of novel therapeutic strategies for alleviating bronchospasm occurring in airway inflammatory diseases.