Ether-à-go-go encodes a voltage-gated channel permeable to K+ and Ca2+ and modulated by cAMP

Abstract

THE Drosophila ether-à-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 channels³, an inward rectifier^4,5 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 perme-ability 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.