PMC

Inhibition of Panx1 channel currents by transport inhibitors. All drugs were applied at a concentration of 500 μM except dipyridamole (200 μM). The experimental procedure was the same as described in legend to .

Effect of α- and β-GA on Panx1 channel currents in Xenopus oocytes. The membrane potential was held at −50 mV and stepped to +50 mV at a rate of 0.1 Hz to elicit Panx1 currents. Both drugs reversibly inhibited currents in oocytes expressing either wtPanx1 or the truncated mutant Panx1, 378stop.

Dose-response curves for inhibition of Panx1 channel currents in Xenopus oocytes by various drugs. Oocytes expressing Panx1 were voltage clamped and the membrane potential was held at −50 mV. To open Panx1 channels repetitive brief voltage steps to + 50 mV were applied. The drugs were applied to the bath by perfusion.

ATP feedback loops controlling Panx1 channels. ATP from an external source activates the P2X7 receptor (P2X7R), which in turn activates by a presently unknown mechanism Panx1. The open Panx1 channel allows the efflux of ATP following its concentration gradient. ATP binds to Panx1 at the extracellular surface with lower affinity than to the P2X7R, inhibiting further ATP release through the Panx1 channel.

Effect of malaria drugs on Panx1 functions. a) Inhibition of Panx1 channel currents in Xenopus oocytes by artesunate is dose dependent with an IC 50 of 450 μM. b) Ethidium bromide uptake into frog erythrocytes was inhibited by artemisinin with an IC50 of 0.14 μM. Dye uptake was determined as described in except ethidium bromide replaced YoPro. unstim. = unstimulated. KGlu = 60 mM potassium gluconate replacing Na⁺ in oocyte Ringer solution. N = 5 for all conditions.

Effects of bongkrekic acid and atractyloside on Panx1 functions. a) atractyloside induces reversible inhibition of Panx1 channel currents in a dose dependent fashion. b) uptake of Ethidium bromide by (nucleated) frog erythrocytes induced by high extracellular K⁺ (60 mM). Inhibition of dye uptake by 4 μM bongkrekic acid (c) and 50 μM atractyloside (d). Dose response curves for inhibition of Panx1 channel currents in Xenopus oocytes by bongkrekic acid (e) and atractyloside (f) (n=5 for all points). The experimental procedure was the same as described in legend to .