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 channel polypeptides expressed in the excitable cells of organisms ranging from invertebrates to mammals. Earlier studies demonstrated that eag mutations in Drosophila cause an increase in membrane excitability in the nervous system. Mutations in the human eag-related gene (HERG) have been implicated in cardiac arrhythmia, and recent studies show that HERG subunits contribute to the channels mediating IKr and the terminal repolarization of the cardiac action potential. A physiological role for M-EAG, the mouse counterpart to Drosophila eag, has not been determined. Here, we describe basic properties of Eag and M-EAG channels expressed in frog oocytes, using two-electrode voltage clamp and patch clamp techniques. Both Eag and M-EAG channels are voltage-dependent, outwardly rectifying and highly selective for K+ over Na+ over Na+ ions. In contrast to previous reports, we found no evidence for Ca2+ flux through Eag channels. The most notable difference between these closely related channels is that Eag currents exhibit partial inactivation, whereas M-EAG currents are sustained for the duration of an activating voltage command. In addition, Eag 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 Eag and M-EAG channels in vivo.