Identification of a mammalian target of κM-conotoxin RIIIK
| Autor: | Ahmed Al-Sabi, Baldomero M. Olivera, Heinrich Terlau, Martin Stocker, Michael Ferber |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Potassium Channels
Conus radiatus Xenopus Snails Peptide Toxicology complex mixtures Conus Kv1.2 Potassium Channel Potassium Channel Blockers Animals Humans Conotoxin Shaker chemistry.chemical_classification Dose-Response Relationship Drug biology urogenital system Inward-rectifier potassium ion channel biology.organism_classification Potassium channel Electrophysiology Kinetics nervous system Biochemistry chemistry Potassium Channels Voltage-Gated Shaker Superfamily of Potassium Channels Biophysics biological phenomena cell phenomena and immunity Conotoxins |
| Zdroj: | Toxicon. 43:915-921 |
| ISSN: | 0041-0101 |
| Popis: | Despite the great variability of the conus peptides characterized until now only relatively few have been identified that interact with K+ channels. kappaM-conotoxin RIIIK (kappaM-RIIIK) is a 24 amino acid peptide from Conus radiatus, which is structurally similar to micro-conotoxin GIIIA, a peptide known to block specifically skeletal muscle Na+ channels. Recently, it has been shown that kappaM-RIIIK does not interact with Na) channels, but inhibits Shaker potassium channels expressed in Xenopus oocytes. It was demonstrated that kappaM-RIIIK binds to the pore region of Shaker channels and a teleost homologue of the Shaker channel TSha1 was identified as a high affinity target of the toxin. In contrast the mammalian Shaker-homologues Kv1.1, Kv1.3, Kv1.4 are not affected by the toxin. In this study the activity of kappaM-RIIIK on other mammalian Kv1 K+ channels expressed in Xenopus oocytes was investigated. We demonstrate that kappaM-conotoxin RIIIK up to 5 microM exhibits no significant effect on Kv1.5 and Kv1.6 mediated currents, but the human Kv1.2 K+ channel is blocked by this peptide. The binding of kappaM-RIIIK to Kv1.2 channels is state dependent with an IC50 for the closed state of about 200 nM and for the open state of about 400 nM at a test potential of 0 mV. kappaM-conotoxin RIIIK is the first conotoxin described to block human Kv1.2 potassium channels. |
| Databáze: | OpenAIRE |
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