RGD Reference Report - Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. - Rat Genome Database

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Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies.

Authors: Escoubas, Pierre  Diochot, Sylvie  Célérier, Marie-Louise  Nakajima, Terumi  Lazdunski, Michel 
Citation: Escoubas P, etal., Mol Pharmacol. 2002 Jul;62(1):48-57. doi: 10.1124/mol.62.1.48.
RGD ID: 405650315
Pubmed: PMID:12065754   (View Abstract at PubMed)
DOI: DOI:10.1124/mol.62.1.48   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
delayed rectifier potassium channel activity enablesIDA 405650315PMID:12065754UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Kcnb1  (potassium voltage-gated channel subfamily B member 1)


Additional Information