Atypical Phenotypes From Flatworm Kv3 Channels

Abstract

Divergence of the Shaker superfamily of voltage-gated (Kv) ion channels early in metazoan evolution created numerous electrical phenotypes that were presumably selected to produce a wide range of excitability characteristics in neurons, myocytes, and other cells. A comparative approach that emphasizes this early radiation provides a comprehensive sampling of sequence space that is necessary to develop generally applicable models of the structure–function relationship in the Kv potassium channel family. We have cloned and characterized two Shaw-type potassium channels from a flatworm ( Notoplana atomata) that is arguably a representative of early diverging bilaterians. When expressed in Xenopus oocytes, one of these cloned channels, N.at-Kv3.1, exhibits a noninactivating, outward current with slow opening kinetics that are dependent on both the holding potential and the activating potential. A second Shaw-type channel, N.at-Kv3.2, has very different properties, showing weak inward rectification. These results demonstrate that broad phylogenetic sampling of proteins of a single family will reveal unexpected properties that lead to new interpretations of structure–function relationships.