Dynamic Selectivity Filters in Ion Channels

Abstract

Membrane ion channels contain integral pores that precisely select their permeant ions. This selectivity anchors our concepts of transmembrane signaling in many tissues, including the nervous system. Excitable cells have a rich repertoire of dynamically regulated channels, and this richness and plasticity allows them to use channels beautifully to suit their needs. The selectivity of ion channel pores has generally been viewed as fixed. However, recent studies on disparate classes of ion channels challenge the generality of this idea and show that some ion channels can change their ion selectivity such that normally impermeant ions do in fact permeate under some circumstances. In no case is the mechanism fully understood, but the phenomenon represents both a new functional aspect of ion channels and a suggestion about novel ways in which channels may process information in the nervous system. This review seeks to highlight studies on ion channels that show selectivity changes, point to possible mechanisms, and draw on common themes. We consider P2X and proton-gated channels from the superfamily of transmitter-gated ion channels, Kv and cardiac sodium channels from the superfamily of voltage-gated ion channels, and cyclic nucleotide–gated channels from the family of channels that are gated by intracellular messengers (Figure 1).