<p>Potassium channels are the most diverse group of the ion channel family[<cite idref="PUB00001055"/>, <cite idref="PUB00001622"/>]. They are important in shaping the action potential, and in neuronal excitability and plasticity [<cite idref="PUB00004020"/>]. The potassium channel family iscomposed of several functionally distinct isoforms, which can be broadlyseparated into 2 groups [<cite idref="PUB00006577"/>]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.</p><p>These are all highly similar proteins, with only small amino acidchanges causing the diversity of the voltage-dependent gating mechanism,channel conductance and toxin binding properties. Each type of K⁺ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins orother second messengers [<cite idref="PUB00004011"/>]. In eukaryotic cells, K⁺ channelsare involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [<cite idref="PUB00002771"/>]. In prokaryotic cells, they play a role in themaintenance of ionic homeostasis [<cite idref="PUB00009378"/>].</p><p> All K⁺ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which hasbeen termed the K⁺ selectivity sequence.In families that contain one P-domain, four subunits assemble to form a selective pathway for K⁺ across the membrane.However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K⁺ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K⁺ channels; and three types of calcium (Ca)-activated K⁺ channels (BK, IK and SK)[<cite idref="PUB00009378"/>]. The 2TM domain family comprises inward-rectifying K⁺ channels. In addition, there are K⁺ channel alpha-subunits that possess two P-domains. These are usually highly regulated K⁺ selective leak channels.</p><p>The first EAG K+ channel was identified in <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, <taxon tax_id="6239">Caenorhabditis elegans</taxon> appears to lack the ELK type [<cite idref="PUB00007312"/>].</p><p>The EAG subfamily has been expressed in heterologous systems to reveal their biophysical and pharmacological functions and to determine their currents in native tissues. All mammalian EAG subfamily K+ channels that have been identified have properties typical of delayed rectifiers, with no measurable inactivation [<cite idref="PUB00008879"/>]. Only the <taxon tax_id="7227">Drosophila melanogaster</taxon> Eag channel exhibits partial inactivation.</p> Potassium channel, voltage-dependent, EAG