Pannexin1 channels act downstream of P2X7receptors in ATP-induced murine T-cell death

• DOI: 10.4161/chan.28122
• Publication Date: 2014-03-04T00:38:26Z
• Authors: Kenji F Shoji; Pablo J Sáez; Paloma A Harcha; Hector L Aguila; Juan C Sáez
• Keywords: Pannexin; Connexon

Death of murine T cells induced by extracellular ATP is mainly triggered activation purinergic P2X7 receptors (P2X7Rs). However, a link between P2X7Rs and pannexin1 (Panx1) channels, which are non-selective, has been recently demonstrated in other cell types. In this work, we characterized the expression cellular distribution pannexin family members (Panxs 1, 2 3) isolated cells. Panx1 was main member clearly detected both helper (CD4+) cytotoxic (CD8+) cells, whereas low levels Panx2 were found T-cell subsets. Using pharmacological genetic approaches, channels to mediate most ATP-induced ethidium uptake since drastically reduced channel blockers (10Panx1, Probenecid carbenoxolone concentration) absent derived from Panx1−/− mice. Moreover, electrophysiological measurements wild-type CD4+ treated with unitary current events sensitivity compatible found. addition, release 4Br-A23187, calcium ionophore, completely blocked inhibitors connexin hemichannels channels. mortality, indicating that death. mortality not mice, intracellular free Ca2+ responses enhanced suggesting take over lose-function mediating onset death ATP.