POTASSIUM CURRENTS EXPRESSED FROM DROSOPHILA AND MOUSE EAG CDNAS IN XENOPUS OOCYTES

The ether-a-go-go (eag) gene family encodes a set of related ion chann el polypeptides expressed in the excitable cells of organisms ranging from invertebrates to mammals. Earlier studies demonstrated that eag m utations in Drosophila cause an increase in membrane excitability in t he nervous system. Mutations in the human eag-related gene (HERG) have been implicated in cardiac arrhythmia, and recent studies show that H ERG subunits contribute to the channels mediating I-Kr and the termina l repolarization of the cardiac action potential. A physiological role for M-EAG, the mouse counterpart to Drosophila eag, has not been dete rmined. Here, we describe basic properties of Lag and M-EAG channels e xpressed in frog oocytes, using two-electrode voltage clamp and patch clamp techniques. Both fag and M-EAG channels are voltage-dependent, o utwardly rectifying and highly selective for K+ over Na+ ions. In cont rast to previous reports, we found no evidence for Ca2+ flux through f ag channels. The most notable difference between these closely related channels is that fag currents exhibit partial inactivation, whereas M -EAG currents are sustained for the duration of an activating voltage command. In addition, Lag currents run down more rapidly than do M-EAG currents in excised macropatches. Rundown is reversible by inserting the patch into the interior of the oocyte, indicating that a cytosolic factor regulates channel activity or stability. These studies should facilitate identification of currents mediated by fag and M-EAG channe ls in vivo. Copyright (C) 1996 Published by Elsevier Science Ltd