AA sequence: Ala-Phe-Cys3-Asn-Leu-Arg-Dab-Cys8-Gln-Leu-Ser-Cys12-Arg-Ser-Leu-Gly-Leu-Leu-Gly-Lys-Cys21-Ile-Gly-Asp-Lys-Cys26-Glu-Cys28-Val-Lys-His-NH2
Disulfide bonds between: Cys3-Cys21, Cys8-Cys 26 and Cys12-Cys28
Length (aa) : 31
Formula: C141H236N46O39S6
Molecular Weight: 3392.12 Da
Appearance: White lyophilized solid
Solubility: water and saline buffer
CAS number: [1061556-49-7]
Source: Synthetic
Purity rate: > 95%
Leiurotoxin-1 Dab7
SK2 channel blocker
Leiuorotoxin-Dab7 (Lei-Dab7) is a mutated version of Leiurotoxin, a peptide identified from the venom of the scorpion Leiurus quinquestriatus hebraeus. The Dab amino acid in position 7 confers to this compound a high selectivity for SK2 channels among other channels. Lei-Dab7 exhibits > 200 fold selectivity for SK2 over SK1, SK3, IK, Kv and Kir channels. The IC50 for SK2 is about 3 nM.
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Correspondences between the binding characteristics of a non-natural peptide, Lei-Dab7
Small-conductance calcium-activated potassium channels (SK1-SK3 channels) are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal firing and integration signal. Two peptide toxins: apamin and Leiurotoxin 1, block this SK channels with high affinities. We generated a modified Leiurotoxin 1 (Lei-Dab7) that inhibits SK2 channels with a high selectivity. Competitive binding of radio-iodinated apamin to different rat brain structures, in the presence of native apamin and Lei-Dab7, has shown that dissociation constants differ by a factor of 1000 and thus demonstrated that ligand affinity is as important as ligand selectivity for a specific receptor. However, the lack of ligands discriminating between SK channel subunits is impeding the understanding of the role of each heteromeric SK channel type in different tissues. Our study aims to better understand the molecular combinations of SK channels and their association with specific functional implications. On this purpose, a clustering technique allows us to identify five groups of brain structures reflecting singular profiles of affinity and selectivity of Lei-Dab7 in comparison with apamin. The analysis of correspondences between Lei-Dab7 binding and distribution of SK subunits in these groups of brain structures suggests that functional heteromeric SK channels are involved in specific information processes.
Aidi-Knani S., et al. (2015) Correspondences between the binding characteristics of a non-natural peptide, Lei-Dab7, and the distribution of SK subunits in the rat central nervous system. Eur J Pharmacol. PMID: 25704615
Small-conductance Ca2+-activated potassium type 2 channels regulate the formation of contextual fear memory
Murthy SR., et al. (2015) Small-conductance Ca2+-activated potassium type 2 channels regulate the formation of contextual fear memory. PLoS One. PMID: 25938421
Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist.
It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.
Regaya I., et al. (2004) Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist. Life Sci. PMID: 15530499