ETHER-A-GO-GO ENCODES A VOLTAGE-GATED CHANNEL PERMEABLE TO K+ AND CA2+ AND MODULATED BY CAMP

THE Drosophila ether-a-go-go (eag) mutant is responsible for altered potassium currents in excitable tissue1. These mutants exhibit spontaneous, repetitive firing of action potentials in the motor axons of larval neuromuscular junctions2. The eag gene encodes a polypeptide3 that shares sequence similarities with several different ionic channel proteins, including voltage-gated potassium channels-, an inward rectifier4,5 as well as cyclic-nucleotide-gated channels6. These formal similarities in the derived primary sequences indicate that eag polypeptides might express a new type of ion channel. Here we report the expression by eag RNA in Xenopus oocytes of such a channel which incorporates properties of both voltage- and ligand-gated channels. The permeability of these eag channels to potassium and calcium is dependent on voltage and cyclic AMP. The ability to mediate potassium-outward and calcium-inward currents endows this channel with properties likely to be important in the modulation of synaptic efficiency in both central and peripheral nervous systems.