The Journal of Neuroscience, April 15, 1999, 19(8):2906-2918
Functional Analysis of a Mouse Brain Elk-Type K+
Channel
Matthew C.
Trudeau1,
Steven A.
Titus2,
Janet L.
Branchaw1,
Barry
Ganetzky2, and
Gail A.
Robertson1
1 Department of Physiology, University of
Wisconsin-Madison Medical School, and 2 Laboratory of
Genetics, University of Wisconsin, Madison, Wisconsin 53706
Members of the Ether à 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 the
Eag and Erg subfamilies have been described, and based on their
characteristic features and expression patterns, Erg channels have been
associated with native currents in the heart. Little is known about the
properties of channels from the Elk subfamily. We have identified a
mouse gene, Melk2, that encodes a predicted polypeptide
with 48% amino acid identity to Drosophila Elk but only
40 and 36% identity with mouse Erg (Merg) and Eag (Meag),
respectively. Melk2 RNA appears to be expressed at high
levels only in brain tissue. Functional expression of Melk2 in Xenopus oocytes reveals large,
transient peaks of current at the onset of depolarization. Like Meag
currents, Melk2 currents activate relatively quickly, but they lack the
nonsuperimposable Cole-Moore shift characteristic of the Eag
subfamily. Melk2 currents are insensitive to E-4031, a class III
antiarrhythmic compound that blocks the Human
Ether-à-go-go-Related Gene (HERG) channel and its counterpart in
native tissues, IKr. Melk2 channels exhibit inward
rectification because of a fast C-type inactivation mechanism, but the
slower rate of inactivation and the faster rate of activation results
in less inward rectification than that observed in HERG channels. This
characterization of Melk currents should aid in identification of
native counterparts to the Elk subfamily of channels in the nervous system.
Key words:
Melk2; Elk; Eag; brain; channel; C-type inactivation
Copyright © 1999 Society for Neuroscience 0270-6474/99/1982906-13$05.00/0