FUNCTIONAL EXPRESSION OF A RAT HOMOLOG OF THE VOLTAGE-GATED ETHER A GO-GO POTASSIUM CHANNEL REVEALS DIFFERENCES IN SELECTIVITY AND ACTIVATION KINETICS BETWEEN THE DROSOPHILA CHANNEL AND ITS MAMMALIAN COUNTERPART

We have cloned a mammalian (rat) homologue of Drosophila ether a go-go (eag) cDNA, which encodes a distinct type of voltage activated potass ium (K) channel, The derived Drosophila and rat eag polypeptides share >670 amino acids, with a sequence identity of 61%, exhibiting a high degree of similarity at the N-terminus, the hydrophobic core including the pore forming P region and a potential cyclic nucleotide binding s ite. Rat eag mRNA is specifically expressed in the central nervous sys tem. In the Xenopus oocyte expression system rat eag mRNA gives rise t o voltage activated K channels which have distinct properties in compa rison with Drosophila eag channels and other voltage activated K chann els. Thus, the rat eag channel further extends the known diversity of K channels. Most notably, the kinetics of rat eag channel activation d epend strongly on holding membrane potential. Hyperpolarization slows down the kinetics of activation; conversely depolarization accelerates the kinetics of activation. This novel K channel property may have im portant implications in neural signal transduction allowing neurons to tune their repolarizing properties in response to membrane hyperpolar ization.