Pore dilation of neuronal P2X receptor channels

P2X receptors are ligand-gated ion channels activated by the binding of extracellular adenosine 5'-triphosphate (ATP). Brief (< 1 s) applications of ATP to nodose ganglion neurons or to cells transfected with P2X(2) or P2X(4) receptor cDNAs induce the opening of a channel selectively permeable to small cations within milliseconds. We now show that, during longer ATP application (10-60 s), the channel also becomes permeable to much larger cations such as N-methyl-D-glucamine and the propidium analog YO-PRO-1. This effect is enhanced in P2X(2) receptors carrying point mutations in the second transmembrane segment. Progressive dilation of the ion-conducting pathway during prolonged activation reveals a mechanism by which ionotropic receptors may alter neuronal function.