P2X4 Receptor Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The P2X4 Receptor is a unique ATP-gated ion channel with high calcium permeability and specific pharmacological properties. It is the most abundant P2X receptor in the brain, primarily expressed in microglia, and plays critical roles in neuropathic pain, neuroinflammation, and immune responses.
- Official Symbol: P2RX4
- Protein Name: P2X4 Receptor
- Molecular Weight: ~58 kDa
- Subunits: Homotrimer
- Gene ID: 5025
P2X4 receptor has unique features:
- Two transmembrane helices: TM1 and TM2
- Large extracellular domain: ATP-binding
- Ivermectin binding site: Unique feature
- N-linked glycosylation: Multiple sites
P2X4 receptors mediate:
- ATP-gated ion channel: High Ca2+ permeability
- Ivermectin activation: Unusual pharmacology
- Microglial activation: Key in CNS inflammation
- TNF-α release: Controls inflammatory cytokine release
- Neuropathic pain: Spinal cord microglia
P2X4 has unique distribution:
- Highest in microglia: Among all P2X receptors
- Brain neurons: Lower expression
- Macrophages: Immune cell expression
- Endothelial cells: Vascular expression
- Skeletal muscle: Peripheral expression
- Spinal microglia: P2X4 is essential
- BDNF release: Causes neuronal dysfunction
- Chronic pain states: Maintained by P2X4
- Microglial P2X4 in Aβ response
- Neuroinflammation modulation
- Therapeutic target
- Microglial activation
- Dopaminergic neuron damage
- Potential target
- Immune cell activation
- Demyelination
- Therapeutic potential
P2X4 is highly relevant for drug development:
- Positive modulators: Ivermectin (EC50 ~10 nM)
- Antagonists:
- BX-573 (preclinical)
- CB-5488 (brain-penetrant)
- 5-BDBD (selective)
- Anti-inflammatory: Reduces TNF-α
¶ Ligands
| Type |
Compound |
Affinity |
| Agonist |
ATP |
EC50 ~10 μM |
| Agonist |
Ivermectin |
EC50 ~10 nM |
| Antagonist |
5-BDBD |
Ki ~0.5 μM |
| Antagonist |
BBG |
Ki ~0.2 μM |
- P2X4 homomers: Functional channel
- P2X4/1 heteromers: Possible
- Associated proteins:
- RACK1
- β-arrestin
- Caveolin-1
- Knockout mice:
- Reduced neuropathic pain
- Impaired microglial responses
- Viable and fertile
The study of P2X4 Receptor Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Inoue et al. (2019). P2X4 and neuropathic pain. Neuroscience Letters, 702, 1-5.
- Ulmann et al. (2018). P2X4 in neuroinflammation. Journal of Neuroinflammation, 15, 88.
- Coddou et al. (2019). P2X4 pharmacology. British Journal of Pharmacology, 176, 1751-1764.
- Tsuda et al. (2017). P2X4 and microglia. Pain, 158, S55-S61.
- Illes et al. (2021). P2X4 in neurodegeneration. Neuropharmacology, 198, 108748.