1.A.7.1.6
ATP-gated P2X3 receptor. Tyr-37 stabilizes desensitized states and restricts calcium permeability (Jindrichova et al., 2011).  Exhibits "high affinity desensitization" but slow reactivation from the desensitized state (Giniatullin and Nistri 2013). An endogenous regulator of P2X3 in bladder is the Pirt protein (TC#8.A.64.1.1) Gao et al. 2015).  X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states have been determined (Mansoor et al. 2016). The open state structure harbours an intracellular motif termed the 'cytoplasmic cap', which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. P2X3 receptor antagonism attenuates the progression of heart failure (Lataro et al. 2023).  Standardized Centella asiatica extract ECa 233 alleviates pain hypersensitivity by modulating P2X3 (Wanasuntronwong et al. 2024). When P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors (Lin et al. 2024).