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• W2137809316 abstract "Stimulation of the P2X 7 receptor by ATP induces cell membrane depolarization, increase in intracellular Ca 2+ concentration, and, in most cases, permeabilization of the cell membrane to molecules up to 900 Da. After the activation of P2X 7 , at least two phenomena occur: the opening of low-conductance (8 pS) cationic channels and pore formation. At least two conflicting hypotheses have been postulated to reconcile these findings: 1) the P2X 7 pore is formed as a result of gradual permeability increase (dilation) of cationic channels, and 2) the P2X 7 pore represents a distinct channel, possibly activated by a second messenger and not directly by extracellular nucleotides. In this study, we investigated whether second messengers are necessary to open the pore associated with the P2X 7 receptor in cells that expressed the pore activity by using the patch-clamp technique in whole cell and cell-attached configurations in conjunction with fluorescent imaging. In peritoneal macrophages and 2BH4 cells, we detected permeabilization and single-channel currents in the cell-attached configuration when ATP was applied outside the membrane patch in a condition in which oxidized ATP and Lucifer yellow were maintained within the pipette. Our data support Ca 2+ as a second messenger associated with pore formation because the permeabilization depended on the presence of intracellular Ca 2+ and was blocked by BAPTA-AM. In addition, MAPK inhibitors (SB-203580 and PD-98059) blocked the permeabilization and single-channel currents in these cells. Together our data indicate that the P2X 7 pore depends on second messengers such as Ca 2+ and MAP kinases." @default.
• W2137809316 created "2016-06-24" @default.
• W2137809316 creator A5023871149 @default.
• W2137809316 creator A5034086193 @default.
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• W2137809316 date "2005-02-01" @default.
• W2137809316 modified "2023-10-01" @default.
• W2137809316 title "Are second messengers crucial for opening the pore associated with P2X₇receptor?" @default.
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• W2137809316 doi "https://doi.org/10.1152/ajpcell.00215.2004" @default.
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