P2X purinoceptor 4 (P2RX4) (P2X4)

The P2X purinoceptor 4 (P2X4) is a ligand-gated ion channel that mediates the influx of calcium and sodium ions in response to extracellular ATP binding (UniProt P51570). It is highly expressed in microglia, macrophages, and endothelial cells, playing a pivotal role in neuroinflammation and the development of neuropathic pain (Trang et al., 2012, Nature Reviews Neuroscience). Upon activation in spinal microglia, P2X4 triggers the release of brain-derived neurotrophic factor (BDNF), which causes a shift in neuronal chloride gradients and leads to hyperalgesia. The specific term "chimeric c10" refers to an engineered zebrafish P2X4 construct (zfP2X4-c10) with truncated N- and C-termini, which was used to solve the first high-resolution crystal structures of the P2X receptor family (Kawate et al., 2009, Nature). While P2X4 is a promising therapeutic target for chronic pain, rheumatoid arthritis, and cardiovascular diseases, developing selective ligands is challenging due to its structural homology with other P2X subtypes. Current pharmacological strategies include the use of small-molecule antagonists like NC-2600 and BX430, as well as allosteric modulators like ivermectin (Abdelrahman et al., 2017, Biochemical Pharmacology).

Other names

P2RX4Purinergic receptor P2X4ATP-gated ion channel P2X4P2X receptor subunit 4zfP2X4-c10P2X4 chimeric c10

Antagonism of the ATP-gated ion channel to inhibit cation influx and downstream signaling; Positive allosteric modulation to enhance channel activity.