Extracellular ATP acts on P2X (ATP-activated purinergic receptors, different from GPCRs), and contributes to symptoms (dyspnea, wheezing) and the pathophysiology (airflow limitation, airway hyperresponsiveness) via Ca2+ sensitization related to the RhoA/Rho-kinase processes (Figure 5) [60]. This evidence concerns the gene RHOA and airway hyperresponsiveness.