PT - JOURNAL ARTICLE AU - Zied Landoulsi AU - Francesco Miceli AU - Angelo Palmese AU - Angela Amoresano AU - Gennaro Marino AU - Mohamed El Ayeb AU - Maurizio Taglialatela AU - Rym Benkhalifa TI - Subtype-Selective Activation of K<sub>v</sub>7 Channels by AaTXK<em>β</em><sub>(2–64)</sub>, a Novel Toxin Variant from the <em>Androctonus australis</em> Scorpion Venom AID - 10.1124/mol.113.088971 DP - 2013 Nov 01 TA - Molecular Pharmacology PG - 763--773 VI - 84 IP - 5 4099 - http://molpharm.aspetjournals.org/content/84/5/763.short 4100 - http://molpharm.aspetjournals.org/content/84/5/763.full SO - Mol Pharmacol2013 Nov 01; 84 AB - Kv7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of Kv7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K+ channels. Therefore, we have optimized a combined purification/screening procedure to identify specific modulator(s) of Kv7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ(2–64), a novel variant of AaTXKβ(1–64), in a high-performance liquid chromatography fraction from Aa venom (named P8), which acts as the first peptide activator of Kv7.4 channels. In particular, in both Xenopus oocytes and mammalian Chinese hamster ovary cells, AaTXKβ(2–64), but not AaTXKβ(1–64), hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologously expressed Kv7.4 channels. AaTXKβ(2–64) also activated Kv7.3, Kv7.2/3, and Kv7.5/3 channels, whereas homomeric Kv1.1, Kv7.1, and Kv7.2 channels were unaffected. We anticipate that these results may prove useful in unraveling the novel biologic roles of AaTXKβ(2–64)-sensitive Kv7 channels and developing novel pharmacologic tools that allow subtype-selective targeting of Kv7 channels.