Functional analysis of a mouse brain Elk-type K+ channel

Members of the Ether a go-go (Eag) K+ channel subfamilies Eag, Erg, and Elk are widely expressed in the nervous system, but their neural functions in vivo remain largely unknown. The biophysical properties of channels from th e fag and Erg subfamilies have been described, and based on their character istic features and expression patterns, Erg channels have been associated w ith native currents in the heart. Little is known about the properties of c hannels from the Elk subfamily. We have identified a mouse gene, Melk2, tha t encodes a predicted polypeptide with 48% amino acid identity to Drosophil a Elk but only 40 and 36% identity with mouse Erg (Merg) and Eag (Meag), re spectively. Melk2 RNA appears to be expressed at high levels only in brain tissue. Functional expression of Melk2 in Xenopus oocytes reveals large, tr ansient peaks of current at the onset of depolarization. Like Meag currents , Melk2 currents activate relatively quickly, but they lack the nonsuperimp osable Cole-Moore shift characteristic of the Fag subfamily. Melk2 currents are insensitive to E-4031, a class III antiarrhythmic compound that blocks the Human Ether-a-go-go-Related Gene (HERG) channel and its counterpart in native tissues, I-Kr. Melk2 channels exhibit inward rectification because of a fast C-type inactivation mechanism, but the slower rate of inactivatio n and the faster rate of activation results in less inward rectification th an that observed in HERG channels. This characterization of Melk currents s hould aid in identification of native counterparts to the Elk subfamily of channels in the nervous system.