Tags

Type your tag names separated by a space and hit enter

Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+.
Proc Natl Acad Sci U S A 2013; 110(36):E3455-63PN

Abstract

The identity and forms of activating ligands for ion channels are fundamental to their physiological roles in rapid electrical signaling. P2X receptor channels are ATP-activated cation channels that serve important roles in sensory signaling and inflammation, yet the active forms of the nucleotide are unknown. In physiological solutions, ATP is ionized and primarily found in complex with Mg(2+). Here we investigated the active forms of ATP and found that the action of MgATP(2-) and ATP(4-) differs between subtypes of P2X receptors. The slowly desensitizing P2X2 receptor can be activated by free ATP, but MgATP(2-) promotes opening with very low efficacy. In contrast, both free ATP and MgATP(2-) robustly open the rapidly desensitizing P2X3 subtype. A further distinction between these two subtypes is the ability of Mg(2+) to regulate P2X3 through a distinct allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP(2-) and weak regulation by Mg(2+). These results reveal the existence of two classes of homomeric P2X receptors with differential sensitivity to MgATP(2-) and regulation by Mg(2+), and demonstrate that both restraining mechanisms can be disengaged in heteromeric channels to form fast and sensitive ATP signaling pathways in sensory neurons.

Authors+Show Affiliations

Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. mufeng_li@nih.gov

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

23959888

Citation

Li, Mufeng, et al. "Subtype-specific Control of P2X Receptor Channel Signaling By ATP and Mg2+." Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 36, 2013, pp. E3455-63.
Li M, Silberberg SD, Swartz KJ. Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+. Proc Natl Acad Sci USA. 2013;110(36):E3455-63.
Li, M., Silberberg, S. D., & Swartz, K. J. (2013). Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+. Proceedings of the National Academy of Sciences of the United States of America, 110(36), pp. E3455-63. doi:10.1073/pnas.1308088110.
Li M, Silberberg SD, Swartz KJ. Subtype-specific Control of P2X Receptor Channel Signaling By ATP and Mg2+. Proc Natl Acad Sci USA. 2013 Sep 3;110(36):E3455-63. PubMed PMID: 23959888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+. AU - Li,Mufeng, AU - Silberberg,Shai D, AU - Swartz,Kenton J, Y1 - 2013/08/19/ PY - 2013/8/21/entrez PY - 2013/8/21/pubmed PY - 2013/12/18/medline KW - magnesium ATP KW - magnesium regulation SP - E3455 EP - 63 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 110 IS - 36 N2 - The identity and forms of activating ligands for ion channels are fundamental to their physiological roles in rapid electrical signaling. P2X receptor channels are ATP-activated cation channels that serve important roles in sensory signaling and inflammation, yet the active forms of the nucleotide are unknown. In physiological solutions, ATP is ionized and primarily found in complex with Mg(2+). Here we investigated the active forms of ATP and found that the action of MgATP(2-) and ATP(4-) differs between subtypes of P2X receptors. The slowly desensitizing P2X2 receptor can be activated by free ATP, but MgATP(2-) promotes opening with very low efficacy. In contrast, both free ATP and MgATP(2-) robustly open the rapidly desensitizing P2X3 subtype. A further distinction between these two subtypes is the ability of Mg(2+) to regulate P2X3 through a distinct allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP(2-) and weak regulation by Mg(2+). These results reveal the existence of two classes of homomeric P2X receptors with differential sensitivity to MgATP(2-) and regulation by Mg(2+), and demonstrate that both restraining mechanisms can be disengaged in heteromeric channels to form fast and sensitive ATP signaling pathways in sensory neurons. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/23959888/Subtype_specific_control_of_P2X_receptor_channel_signaling_by_ATP_and_Mg2+_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=23959888 DB - PRIME DP - Unbound Medicine ER -