Potassium channel, voltage-dependent, ELK <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>Little is known about the properties of channels of the ELK subfamily. However, when expressed in frog oocytes, they show properties between those of the EAG and ERG subtypes. Included in this family are Bec1 and Bec2, brain-specific genes found in the human telencephalon regions. It is thought that they are involved in cellular excitability of restricted neurons in the human central nervous system. Phylogenetic analysis reveals that these genes constitute a subfamily with Elk within the Eag family [<cite idref="PUB00008881"/>]. Recently, a further Elk subfamily member has been identified in the mouse (Melk). On the basis of sequence similarity, this indicates a distinct subclass within this family [<cite idref="PUB00008882"/>].</p>