title: Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System.
abstract: The P2X purinergic receptors are cation-selective channels gated by extracellular adenosine 5'-triphosphate (ATP). These purinergic receptors are found in virtually all mammalian cell types and facilitate a number of important physiological processes. Within the past few years, the characterization of crystal structures of the zebrafish P2X4 receptor in its closed and open states has provided critical insights into the mechanisms of ligand binding and channel activation. Understanding of this gating mechanism has facilitated to design and interpret new modeling and structure-function experiments to better elucidate how different agonists and antagonists can affect the receptor with differing levels of potency. This review summarizes the current knowledge on the structure, activation, allosteric modulators, function, and location of the different P2X receptors. Moreover, an emphasis on the P2X2 receptors has been placed in respect to its role in the auditory system. In particular, the discovery of three missense mutations in P2X2 receptors could become important areas of study in the field of gene therapy to treat progressive and noise-induced hearing loss. J. Cell. Physiol. 231: 1656-1670, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Brandon
authors.initials: B
authors.lastname: Chan
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: M'hamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Jeenu
authors.initials: J
authors.lastname: Mittal
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Kunal
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Luca H
authors.initials: LH
authors.lastname: Debs
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Amit P
authors.initials: AP
authors.lastname: Patel
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Physics, Florida International University, Miami, Florida.|Biomolecular Science Institute, Florida International University, Miami, Florida.
authors.forename: Prem
authors.initials: P
authors.lastname: Chapagain
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.|Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.|Department of Biochemistry, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006309:Hearing / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D008958:Models, Molecular; D020125:Mutation, Missense; D010641:Phenotype; D011487:Protein Conformation; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D058469:Receptors, Purinergic P2X / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate