title: Na+ modulates anion permeation and block of P2X7 receptors from mouse parotid glands.
abstract: We previously reported that mouse parotid acinar cells display anion conductance (I(ATPCl)) when stimulated by external ATP in Na+-free extracellular solutions. It has been suggested that the P2X7 receptor channel (P2X7R) might underlie I(ATPCl). In this work we show that I (ATPCl) can be activated by ATP, ADP, AMP-PNP, ATPgammaS and CTP. This is consistent with the nucleotide sensitivity of P2X7R. Accordingly, acinar cells isolated from P2X7R( -/- ) mice lacked I(ATPCl). Experiments with P2X7R heterologously expressed resulted in ATP-activated currents (I(ATP-P2X7)) partially carried by anions. In Na(+)-free solutions, I (ATP-P2X7) had an apparent anion permeability sequence of SCN(-) > I(-) congruent with NO3(-) > Br(-) > Cl(-) > acetate, comparable to that reported for I(ATPCl) under the same conditions. However, in the presence of physiologically relevant concentrations of external Na+, the Cl(-) permeability of I(ATP-P2X7) was negligible, although permeation of Br(-) or SCN(-) was clearly resolved. Relative anion permeabilities were not modified by addition of 1 mM: carbenoxolone, a blocker of Pannexin-1. Moreover, cibacron blue 3GA, which blocks the Na(+) current activated by ATP in acinar cells but not I(ATPCl), blocked I(ATP-P2X7) in a dose-dependent manner when Na+ was present but failed to do so in tetraethylammonium containing solutions. Thus, our data indicate that P2X7R is fundamental for I(ATPCl) generation in acinar cells and that external Na+ modulates ion permeability and conductivity, as well as drug affinity, in P2X7R.
authors.affiliation: Instituto de Física, Universidad Autónoma de San Luis Potosí, Dr. Manuel Nava #6, San Luis Potosi, SLP 78290, Mexico.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Reyes
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Cornejo
authors.forename: Carmen Y
authors.initials: CY
authors.lastname: Hernández-Carballo
authors.forename: Alaka
authors.initials: A
authors.lastname: Srivastava
authors.forename: Victor G
authors.initials: VG
authors.lastname: Romanenko
authors.forename: Mireya
authors.initials: M
authors.lastname: Gonzalez-Begne
authors.forename: James E
authors.initials: JE
authors.lastname: Melvin
authors.forename: Jorge
authors.initials: J
authors.lastname: Arreola
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010539:Permeability / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D012964:Sodium / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology
chemical_list: D000227:Adenine Nucleotides; D000838:Anions; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D014227:Triazines; C012842:Cibacron Blue F 3GA; D000255:Adenosine Triphosphate; D012964:Sodium