Fig. 2

TRPV4-ATP-P2X3 pathway involved in the cough response. Proposed mechanism involves the activation of TRPV4 by hypotonic solutions, irritant or known agonist, leading to the influx of calcium ions into the cytosol (1). Activation of TRPV4 and the increase in intracellular calcium, leads to the release of ATP into the extracellular space mediated by pannexin-1 (2). Extracellular ATP activates P2X3 on sensory neurons creating an action potential in the sensory neurons of the airways (3) which may subsequently trigger the cough reflex (4)