Figure 4.

Allosteric modulators induced changes in the pore radius of the extracellular P2X4R vestibule in different states of the P2X4R. (A) Pore dimensions obtained during the last 10 ns MD simulations of the P2X4R in apo or holo state, holo with Zn(II) or with IVM, and the holo P2X4R with both IVM and Zn(II), along the vestibular portions of the P2X4R. (B) Representative tracings obtained in a single oocyte expressing the wt P2X4R following 1 μM ATP-evoked currents in the absence of modulators, and following incubation with either 10 μM Zn(II), 3 μM IVM, or the joint application of IVM plus Zn(II). In all cases 1 μM ATP-evoked currents were recorded (blue rectangles), while IVM applications are shown in brown rectangles.