Pannexin1 channels act downstream of P2X(7) receptors in ATP-induced murine T-cell death

Shoji KF, Sáez PJ, Harcha PA, Aguila HL, Sáez JC.


Death of murine T cells induced by extracellular ATP is mainly triggered by activation of purinergic P2X7 receptors (P2X(7)Rs). However, a link between P2X(7)Rs and pannexin1 (Panx1) channels, which are non-selective, has been recently demonstrated in other cell types. In this work, we characterized the expression and cellular distribution of pannexin family members (Panxs 1, 2 and 3) in isolated T cells. Panx1 was the main pannexin family member clearly detected in both helper (CD4(+)) and cytotoxic (CD8(+)) T cells, whereas low levels of Panx2 were found in both T-cell subsets. Using pharmacological and genetic approaches, Panx1 channels were found to mediate most ATP-induced ethidium uptake since this was drastically reduced by Panx1 channel blockers ((10)Panx1, Probenecid and low carbenoxolone concentration) and absent in T cells derived from Panx1(-/-)mice. Moreover, electrophysiological measurements in wild-type CD4(+) cells treated with ATP unitary current events and pharmacological sensitivity compatible with Panx1 channels were found. In addition, ATP release from T cells treated with 4Br-A23187, a calcium ionophore, was completely blocked with inhibitors of both connexin hemichannels and Panx1 channels. Panx1 channel blockers drastically reduced the ATP-induced T-cell mortality, indicating that Panx1 channels mediate the ATP-induced T-cell death. However, mortality was not reduced in T cells of Panx1(-/-)mice, in which levels of P2X(7)Rs and ATP-induced intracellular free Ca2+ responses were enhanced suggesting that P2X(7)Rs take over Panx1 channels lose-function in mediating the onset of cell death induced by extracellular ATP.

Más información

Título según WOS: Pannexin1 channels act downstream of P2X(7) receptors in ATP-induced murine T-cell death
Título según SCOPUS: Pannexin1 channels act downstream of P2X7 receptors in ATP-induced murine T-cell death
Título de la Revista: CHANNELS
Volumen: 8
Número: 2
Fecha de publicación: 2014
Página de inicio: 142
Página final: 156
Idioma: English


Notas: ISI, SCOPUS - Scopus