A Functional Connection Between the Pores of Distantly Related Ion Channels as Revealed by Mutant K + Channels

Abstract

The overall sequence similarity between the voltage-activated K + channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K + channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K + channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K + selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K + , Ca 2+ , and cyclic nucleotide-gated ion channels.