Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds

Fast synaptic transmission depends on the selective ionic permeability of t ransmitter-gated ion channels. Here we show changes in the ion selectivity of neuronal P2X transmitter-gated cation channels as a function of time (on the order of seconds) and previous ATP exposure. Heterologously expressed P2X2 P2X2/P2X3 and P2X4 channels as well as native neuronal P2X channels po ssess various combinations of mono- or biphasic responses and permeability changes, measured by NMDG(+) and fluorescent dye. Furthermore, in P2X4 rece ptors, this ability to alter ion selectivity can be increased or decreased by altering an amino-acid residue thought to line the ion permeation pathwa y, identifying a region that governs this activity-dependent change.