ArticleThe Journal of general physiology2007
Acidic amino acids impart enhanced Ca2+ permeability and flux in two members of the ATP-gated P2X receptor family.
Article in The Journal of general physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Structural basis for a central permeation pathway in the P2X1 receptor.Cell discovery · 2026Article
- Species Differences of P2X4 Receptor Modulators.ACS pharmacology & translational science · 2025Article
- Article
- The P2X1 receptor as a therapeutic target.Purinergic signalling · 2022Review
- Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models.The Journal of clinical investigation · 2021Article
- Role of Conserved Residues and F322 in the Extracellular Vestibule of the Rat P2X7 Receptor in Its Expression, Function and Dye Uptake Ability.International journal of molecular sciences · 2020Article
- CaThe Journal of biological chemistry · 2019Article
- Purinergic signalling in autoimmunity: A role for the P2X7R in systemic lupus erythematosus?Biomedical journal · 2016Review
- Measurement of relative Ca²⁺ permeability during sustained activation of TRPV1 receptors.Pflugers Archiv : European journal of physiology · 2016Article
- Quantifying Ca2+ current and permeability in ATP-gated P2X7 receptors.The Journal of biological chemistry · 2015Article
- Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis.Current medicinal chemistry · 2015Review
- Regulation of ATP-gated P2X channels: from redox signaling to interactions with other proteins.Antioxidants & redox signaling · 2014Review
- Imaging P2X4 receptor subcellular distribution, trafficking, and regulation using P2X4-pHluorin.The Journal of general physiology · 2014Article
- Principles and properties of ion flow in P2X receptors.Frontiers in cellular neuroscience · 2014Review
- Structural and functional properties of the rat P2X4 purinoreceptor extracellular vestibule during gating.Frontiers in cellular neuroscience · 2014Article
- Primitive ATP-activated P2X receptors: discovery, function and pharmacology.Frontiers in cellular neuroscience · 2013Review
- P2X receptors as drug targets.Molecular pharmacology · 2013Review
- Multiple roles of the extracellular vestibule amino acid residues in the function of the rat P2X4 receptor.PloS one · 2013Article
- Functional identification of close proximity amino acid side chains within the transmembrane-spanning helixes of the P2X2 receptor.PloS one · 2013Article
- Review
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Authors and funding
2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
P2X receptors are ATP-gated cation channels expressed in nerve, muscle, bone, glands, and the immune system. The seven family members display variable Ca2+ permeabilities that are amongst the highest of all ligand-gated channels (Egan and Khakh, 2004). We previously reported that polar residues regulate the Ca2+ permeability of the P2X2 receptor (Migita et al., 2001). Here, we test the hypothesis that the formal charge of acidic amino acids underlies the higher fractional Ca2+ currents (Pf%) of the rat and human P2X1 and P2X4 subtypes. We used patch-clamp photometry to measure the Pf% of HEK-293 cells transiently expressing a range of wild-type and genetically altered receptors. Lowering the pH of the extracellular solution reduced the higher Pf% of the P2X1 receptor but had no effect on the lower Pf% of the P2X2 receptor, suggesting that ionized side chains regulate the Ca2+ flux of some family members. Removing the fixed negative charges found at the extracellular ends of the transmembrane domains also reduced the higher Pf% of P2X1 and P2X4 receptors, and introducing these charges at homologous positions increased the lower Pf% of the P2X2 receptor. Taken together, the data suggest that COO- side chains provide an electrostatic force that interacts with Ca2+ in the mouth of the pore. Surprisingly, the glutamate residue that is partly responsible for the higher Pf% of the P2X1 and P2X4 receptors is conserved in the P2X3 receptor that has the lowest Pf% of all family members. We found that neutralizing an upstream His45 increased Pf% of the P2X3 channel, suggesting that this positive charge masks the facilitation of Ca2+ flux by the neighboring Glu46. The data support the hypothesis that formal charges near the extracellular ends of transmembrane domains contribute to the high Ca2+ permeability and flux of some P2X receptors.
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