Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies
| Autor: | Michel Lazdunski, Pierre Escoubas, Terumi Nakajima, Marie-Louise Célérier, Sylvie Diochot |
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| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Fonctionnement et Evolution des Ecosystèmes, Université Pierre et Marie Curie - Paris 6 (UPMC), Suntory Institute for Bioorganic Research, Suntory Institute, Université Nice Sophia Antipolis (1965 - 2019) (UNS) |
| Rok vydání: | 2002 |
| Předmět: |
Potassium Channels
Molecular Sequence Data Spider Venoms Gating Shab Potassium Channels Biology Sodium Channels SK channel 03 medical and health sciences 0302 clinical medicine Cerebellum medicine Animals Amino Acid Sequence Rats Wistar 030304 developmental biology Pharmacology 0303 health sciences COS cells Sequence Homology Amino Acid Inward-rectifier potassium ion channel Potassium channel blocker Potassium channel Rats 3. Good health Biochemistry Potassium Channels Voltage-Gated Molecular Medicine Calcium Female Inhibitor cystine knot 030217 neurology & neurosurgery Delayed Rectifier Potassium Channels medicine.drug |
| Zdroj: | Molecular Pharmacology Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2002, 62, pp.48-57 Molecular Pharmacology, 2002, 62, pp.48-57 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.62.1.48 |
| Popis: | Three novel peptides with the ability to inhibit voltage-dependent potassium channels in the shab (Kv2) and shal (Kv4) subfamilies were identified from the venom of the African tarantulas Stromatopelma calceata (ScTx1) and Heteroscodra maculata (HmTx1, HmTx2). The three toxins are 34- to 38-amino acid peptides that belong to the structural family of inhibitor cystine knot spider peptides reticulated by three disulfide bridges. Electrophysiological recordings in COS cells show that these toxins act as gating modifier of voltage-dependent K+ channels. ScTx1 is the first high-affinity inhibitor of the Kv2.2 channel subtype (IC50, 21.4 nM) to be described. ScTx1 also inhibits the Kv2.1 channels, with an IC50 of 12.7 nM, and Kv2.1/Kv9.3 heteromultimers that have been proposed to be involved in O2 sensing in pulmonary artery myocytes. In addition, it is the most effective inhibitor of Kv4.2 channels described thus far, with an IC50 of 1.2 nM. HmTx toxins share sequence similarities with both the potassium channel blocker toxins (HmTx1) and the calcium channel blocker toxin omega-GsTx SIA (HmTx2). They inhibit potassium current associated with Kv2 subtypes in the 100 to 300 nM concentration range. HmTx2 seems to be a specific inhibitor of Kv2 channels, whereas HmTx1 also inhibits Kv4 channels, including Kv4.1, with the same potency. HmTx1 is the first described peptide effector of the Kv4.1 subtype. Those novel toxins are new tools for the investigation of the physiological role of the different potassium channel subunits in cellular physiology. |
| Databáze: | OpenAIRE |
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