Sensory transduction in cough-associated nerves

Before a tussive stimulus in the airways can evoke a cough reflex it must first cause action potential discharge in cough-associated vagal sensory nerves. This is initiated by the stimulus first interacting with the receptors and ion channels in the terminal membrane of the sensory fiber in a manner that leads to membrane depolarization. If the stimulus-induced membrane depolarization, referred to as a generator potential, is of sufficient magnitude, action potentials are elicited that are then conducted to the central nervous system. If the action potentials are of sufficient number and frequency, a cough is evoked. The most common tussive stimuli include mechanical perturbations, anosmotic solutions, acidic solutions, and various chemical agents. The mechanisms underlying the transduction of most of these tussive stimuli into a generator potential are only partially understood. In general terms, chemical stimuli interact directly with receptors that are classified as either ligand gated ion channels or metabotropic receptors (e.g. G-protein coupled receptors). Ligand gated receptors are those in which the receptor protein also serves as the ion channel. The metabotropic receptors indirectly modulate the ion channels activity via various signal transduction schemes. Mechanical stimuli are thought to interact with mechanically gated ion channels, and acid can interact with acid sensing ion channels in addition to the capsaicin receptor TRPV1. In this overview some of the specific receptors and ion channels involved in the tussive stimulus-induced generator potentials in vagal afferent nerve terminals are discussed.