Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 May 14;28520:14882-14889. doi: 10.1074/jbc.M109.068486.
Show Gene links
Show Anatomy links
Biochemical characterization of kappaM-RIIIJ, a Kv1.2 channel blocker: evaluation of cardioprotective effects of kappaM-conotoxins.
Chen P, Dendorfer A, Finol-Urdaneta RK, Terlau H, Olivera BM.
???displayArticle.abstract???
Conus snail (Conus) venoms are a valuable source of pharmacologically active compounds; some of the peptide toxin families from the snail venoms are known to interact with potassium channels. We report the purification, synthesis, and characterization of kappaM-conotoxin RIIIJ from the venom of a fish-hunting species, Conus radiatus. This conopeptide, like a previously characterized peptide in the same family, kappaM-RIIIK, inhibits the homotetrameric human Kv1.2 channels. When tested in Xenopus oocytes, kappaM-RIIIJ has an order of magnitude higher affinity (IC(50) = 33 nm) to Kv1.2 than kappaM-RIIIK (IC(50) = 352 nm). Chimeras of RIIIK and RIIIJ tested on the human Kv1.2 channels revealed that Lys-9 from kappaM-RIIIJ is a determinant of its higher potency against hKv1.2. However, when compared in a model of ischemia/reperfusion, kappaM-RIIIK (100 mug/kg of body weight), administered just before reperfusion, significantly reduces the infarct size in rat hearts in vivo without influencing hemodynamics, providing a potential compound for cardioprotective therapeutics. In contrast, kappaM-RIIIJ does not exert any detectable cardioprotective effect. kappaM-RIIIJ shows more potency for Kv1.2-Kv1.5 and Kv1.2-Kv1.6 heterodimers than kappaM-RIIIK, whereas the affinity of kappaM-RIIIK to Kv1.2-Kv1.7 heterodimeric channels is higher (IC(50) = 680 nm) than that of kappaM-RIIIJ (IC(50) = 3.15 mum). Thus, the cardioprotection seems to correlate to antagonism to heteromultimeric channels, involving the Kv1.2 alpha-subunit rather than antagonism to Kv1.2 homotetramers. Furthermore, kappaM-RIIIK and kappaM-RIIIJ provide a valuable set of probes for understanding the underlying mechanism of cardioprotection.
Al-Sabi,
KappaM-conotoxin RIIIK, structural and functional novelty in a K+ channel antagonist.
2004, Pubmed
Al-Sabi,
KappaM-conotoxin RIIIK, structural and functional novelty in a K+ channel antagonist.
2004,
Pubmed Brinckmann,
Interleukin 4 and prolonged hypoxia induce a higher gene expression of lysyl hydroxylase 2 and an altered cross-link pattern: important pathogenetic steps in early and late stage of systemic scleroderma?
2005,
Pubmed Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase Coetzee,
Molecular diversity of K+ channels.
1999,
Pubmed
,
Xenbase Cohen,
The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis.
2007,
Pubmed Dixon,
Potassium channel mRNA expression in prevertebral and paravertebral sympathetic neurons.
1996,
Pubmed Ferber,
Identification of a mammalian target of kappaM-conotoxin RIIIK.
2004,
Pubmed
,
Xenbase Ferber,
A novel conus peptide ligand for K+ channels.
2003,
Pubmed
,
Xenbase Finol-Urdaneta,
Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
2006,
Pubmed
,
Xenbase Gulbis,
The beta subunit of Kv1 channels: voltage-gated enzyme or safety switch?
2002,
Pubmed Hill,
Three-dimensional solution structure of mu-conotoxin GIIIB, a specific blocker of skeletal muscle sodium channels.
1996,
Pubmed Hopkins,
Toxin and subunit specificity of blocking affinity of three peptide toxins for heteromultimeric, voltage-gated potassium channels expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase Imperial,
A novel conotoxin inhibitor of Kv1.6 channel and nAChR subtypes defines a new superfamily of conotoxins.
2006,
Pubmed Jan,
Cloned potassium channels from eukaryotes and prokaryotes.
1997,
Pubmed Kaplan,
Hypercapnic acidosis and dimethyl amiloride reduce reperfusion induced cell death in ischaemic ventricular myocardium.
1995,
Pubmed Keizer,
Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA.
2003,
Pubmed Koch,
The binding of kappa-Conotoxin PVIIA and fast C-type inactivation of Shaker K+ channels are mutually exclusive.
2004,
Pubmed
,
Xenbase Lancelin,
Tertiary structure of conotoxin GIIIA in aqueous solution.
1991,
Pubmed Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase Lubbers,
Postischemic administration of CGX-1051, a peptide from cone snail venom, reduces infarct size in both rat and dog models of myocardial ischemia and reperfusion.
2005,
Pubmed Nesti,
Endocytosis as a mechanism for tyrosine kinase-dependent suppression of a voltage-gated potassium channel.
2004,
Pubmed Nielsen,
Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels.
2002,
Pubmed Olivera,
Conus peptides: biodiversity-based discovery and exogenomics.
2006,
Pubmed Plane,
Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter.
2005,
Pubmed Qiu,
Enhancement of ischemia-induced tyrosine phosphorylation of Kv1.2 by vascular endothelial growth factor via activation of phosphatidylinositol 3-kinase.
2003,
Pubmed Schlüter,
Prevention of the oxygen paradox in hypoxic-reoxygenated hearts.
1991,
Pubmed Shon,
kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel.
1998,
Pubmed
,
Xenbase Terlau,
Conus venoms: a rich source of novel ion channel-targeted peptides.
2004,
Pubmed Terlau,
Strategy for rapid immobilization of prey by a fish-hunting marine snail.
1996,
Pubmed Vacher,
Localization and targeting of voltage-dependent ion channels in mammalian central neurons.
2008,
Pubmed Verdier,
Identification of a novel pharmacophore for peptide toxins interacting with K+ channels.
2005,
Pubmed
,
Xenbase Wolfrum,
Apstatin, a selective inhibitor of aminopeptidase P, reduces myocardial infarct size by a kinin-dependent pathway.
2001,
Pubmed Zhang,
CGX-1051, a peptide from Conus snail venom, attenuates infarction in rabbit hearts when administered at reperfusion.
2003,
Pubmed
