title: The P2X7 receptor: shifting from a low- to a high-conductance channel - an enigmatic phenomenon?
abstract: The general structure of the P2X7 receptor (P2X7R) is similar to the structure of other P2X receptor family members, with the exception of its C terminus, which is the longest of this family. The P2X7R activates several intracellular signaling cascades, such as the calmodulin, mitogen-activated protein kinase and phospholipase D pathways. At low concentrations of ATP (micromolar range), P2X7R activation opens a cationic channel, similarly to other P2X receptors. However, in the presence of high concentrations of ATP (millimolar range), it opens a pathway that allows the passage of larger organic cations and anions. Here, we discuss both the structural characteristics of P2X7R related to its remarkable functions and the proposed mechanisms, including the dilation of the endogenous pore and the integration of another channel. In addition, we highlight the importance of P2X7R as a therapeutic target.
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Luiz Anastacio
authors.initials: LA
authors.lastname: Alves
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ricardo Augusto
authors.initials: RA
authors.lastname: de Melo Reis
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Cristina Alves Magalhães
authors.initials: CA
authors.lastname: de Souza
authors.affiliation: Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Instituto de Bioquímica Médica, Instituto Nacional de Ciências e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Monica Santos
authors.initials: MS
authors.lastname: de Freitas
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Pedro Celso Nogueira
authors.initials: PC
authors.lastname: Teixeira
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Dinarte
authors.initials: D
authors.lastname: Neto Moreira Ferreira
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Comunicação Celular, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Robson Faria
authors.initials: RF
authors.lastname: Xavier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D017434:Protein Structure, Tertiary; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: Calcium; Ion channel activity; P2X7R; Patch-clamp; Second messenger