Table 1. Evidence for different activation mechanisms of Panx1 channels
Activation mechanism and stimulationModel systemElectrophysiologyATP releaseDye permeationReference
Pressure or stretch
Negative pressure (∼40 mbar)Recombinant PANX1 in Xenopus oocytesSingle-channel recording; inhibitor NANANABao et al., 2004
PressureNative PANX1 in human erythrocytesSingle-channel recording; inhibitor NANANALocovei et al., 2006a
Stretch (15 or 30 cmH2O)Native Panx1 in rat bladdersNACBX (100 µM); BB FCF (100 µM)NABeckel et al., 2015
HypotonicityNative PANX1 in human erythrocytesNACBX (100 µM)Inhibitor NALocovei et al., 2006a
HypotonicityNative PANX1 in human bronchial epithelial cellsNACBX (10 µM); 10Panx1 (30 µM)CBX (10 µM); 10Panx1 (30 µM)Seminario-Vidal et al., 2011
HypotonicityNative PANX1 in A549 cellsNAPANX1 siRNAPANX1 siRNASeminario-Vidal et al., 2011
HypotonicityNative Panx1 in mouse tracheasNAPanx1−/−Panx1−/−Seminario-Vidal et al., 2011
HypotonicityNative PANX1 in CN-LM1A and MDA-LM2 cellsaNACBX (500 µM)bNAFurlow et al., 2015
Hypotonicity and 75 mM extracellular K+Native Panx1 in mouse erythrocytesNAProbenecid (1 mM); Panx1−/−±probenecidPanx1−/−Qiu et al., 2011
Extracellular K+
20∼150 mM K+Recombinant Panx1 in Xenopus oocytesWhole-cell current; CBX (100 µM); probenecid (1 mM)CBX (100 µM); probenecid (100 or 500 µM)NASilverman et al., 2009; Wang et al., 2014
150 mM K+Recombinant Panx1 in Xenopus oocytesSingle-channel recording; inhibitor NACBX (100 µM)NAWang et al., 2014
? mM K+Recombinant Panx1 in Xenopus oocytesNABB FCF (10 µM)NAWang et al., 2013
50 mM K+Native PANX1 in 1321N1 cellsNANAPanx1 shRNASilverman et al., 2009
10 mM K+Native Panx1 in mouse hippocampal slidesNAMefloquine (100 nM); Panx1−/−Mefloquine (100 nM); Panx1−/−Santiago et al., 2011
10 mM K+Native Panx1 in mouse astrocytesWhole-cell current; Panx1−/−Panx1−/−Panx1−/−Suadicani et al., 2012
75 mM extracellular K+ and hypotonicityNative Panx1 in mouse erythrocytesNAProbenecid (1 mM); Panx1−/−±probenecidPanx1−/−Qiu et al., 2011
Intracellular Ca2+
Ca2+ (0.1 µM∼10 mM)Recombinant PANX1 in Xenopus oocytesInside-out macropatch; single-channel recording; inhibitor NANANALocovei et al., 2006b
A23187 (200 µM)Recombinant Panx1 in Xenopus oocytesWhole-cell current; inhibitor NANANALocovei et al., 2006b
Ionomycin (10 µM)Recombinant PANX1 in N2A cellsNANAInhibitor NAKurtenbach et al., 2013
Thrombin (30 nM)Native PANX1 in A549 cellsNACBX (10 µM); BAPTA-AM (20 µM); thapsigargin (1 µM)CBX (10 µM); BAPTA-AM (20 µM)Seminario-Vidal et al., 2009
Thrombin (1 or 1,000 U/ml)Native PANX1 in HUVECsNACBX (5 µM); PANX1 shRNA; BAPTA-AM (5 µM)NAGödecke et al., 2012
Caffeine (concentration NA)Recombinant Panx1 in rat atrial myocytesSingle-channel recording; CBX (20 µM); probenecid (200 µM)NANAKienitz et al., 2011
SFK-mediated phosphorylation
NMDA (100 µM)Native Panx1 in rat hippocampal neuronsWhole-cell current; CBX (50 µM); 10Panx1 (100 µM); Panx1 shRNANACBX (50 µM); 10Panx1 (100 µM)Thompson et al., 2008; Weilinger et al., 2016
AnoxiaNative Panx1 in rat CA1 neuronsWhole-cell current; 10Panx1 (100 µM)±APV (50 µM); probenecid (500 µM); brain-specific Panx1−/−; TAT-Panx305-318 peptide (1 or 10 µM)NANAWeilinger et al., 2012
TNFα (10 ng/ml)Native PANX1 in HUVECsNACBX (50 µM); 10Panx1 (200 µM); Panx1 siRNA; endothelial cell–specific Panx1−/−10Panx1 (200 µM)Lohman et al., 2015
TNFα (50 ng/ml)Native Panx1 in mouse venous endotheliaNAEndothelial cell–specific Panx1−/−NALohman et al., 2015
BzATP (50 or 300 µM)Native Panx1 in J774 cellsWhole-cell current; CBX (50 µM); mefloquine (100 nM); Panx1 siRNANACBX (50 µM); mefloquine (10 nM); Panx1 siRNAIglesias et al., 2008
BzATP (300 µM)Recombinant Panx1 in Xenopus oocytesWhole-cell current; inhibitor NANAInhibitor NAIglesias et al., 2008
BzATP (300 µM)Native Panx1 in peritoneal macrophage from A/J miceNANACBX (10 µM); 10Panx1 (300 µM)Sorge et al., 2012
BzATP (300 µM)Native Panx1 in mouse astrocytesWhole-cell current; CBX (50 µM); mefloquine (100 nM); Panx1−/−Panx1−/−Panx1−/−Suadicani et al., 2012
C-tail cleavage
Anti-Fas (5 µg/ml)Native PANX1 in Jurkat cellsWhole-cell current; CBX (10∼500 µM); probenecid (10 µM∼2 mM); CBX (100 µM)+PANX1 siRNACBX (500 µM)c; probenecid (2 mM); PANX1 siRNAPANX1 siRNA; CBX (500 µM)Chekeni et al., 2010
Anti-Fas (5 µg/ml)Native Panx1 in mouse thymocytesNANACBX (500 µM)Chekeni et al., 2010
Anti-Fas (5 µg/ml)Recombinant PANX1 in Jurkat cellsWhole-cell current; caspase site-deficient PANX1; CBX (100 µM)Caspase site-deficient PANX1Caspase site-deficient PANX1Chekeni et al., 2010
Anti-Fas (5 µg/ml)Native Panx1 in mouse thymocytesNANAPanx1−/−Qu et al., 2011
Dexamethasone (0.5 µM)Native Panx1 in mouse thymocytesNAPanx1−/−NAQu et al., 2011
C-tail truncationcRecombinant PANX1 in Jurkat cellsWhole-cell current; CBX (100 µM)NAInhibitor NAChekeni et al., 2010
Caspase 3Native PANX1 in Jurkat cells; Recombinant PANX1 in HEK293T cellsInside-out macropatch; Single-channel recording; CBX (50 µM)NANASandilos et al., 2012; Chiu et al., 2017
TEV proteasedRecombinant PANX1 in HEK293T cellsWhole-cell current; Inside-out macropatch; CBX (50 µM)NAInhibitor NASandilos et al., 2012
LPS (50 ng/ml)Native Panx1 in bone marrow–derived macrophageNACBX (50 µM); probenecid (100 µM); trovafloxacin (100 µM); Panx1−/−NAYang et al., 2015
LPS (50 ng/ml)Recombinant Panx1 in bone marrow–derived macrophageNAPanx1−/− with Panx1-D378ANAYang et al., 2015

NA, data not available or unknown.

  • a The cells endogenously express both wild-type and a truncated form of PANX1, which only expresses amino acid 1-89 of PANX1.

  • b High concentration of CBX is required for inhibition of ATP release if albumin is present in the assay system (Chekeni et al., 2010).

  • c A C-terminal truncated PANX1 (amino acid 1-371) was used in the study.

  • d This study used a mutant human PANX1, with its caspase cleavage site replaced by a TEV protease cleavage site.