Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4.
Sea anemone venom is known to contain toxins that are active on voltage-sensitive Na+ channels, as well as on delayed rectifier K+ channels belonging to the Kv1 family. This report describes the properties of a new set of peptides from Anemonia sulcata that act as blockers of a specific member of the Kv3 potassium channel family. These toxins, blood depressing substance (BDS)-I and BDS-II, are 43 amino acids long and differ at only two positions. They share no sequence homologies with other K+ channel toxins from sea anemones, such as AsKS, AsKC, ShK, or BgK. In COS-transfected cells, the Kv3.4 current was inhibited in a reversible manner by BDS-I, with an IC50 value of 47 nM. This inhibition is specific because BDS-I failed to block other K+ channels in the Kv1, Kv2, Kv3, and Kv4 subfamilies. Inward rectifier K+ channels are also insensitive to BDS-I. BDS-I and BDS-II share the same binding site on brain synaptic membranes, with K0.5 values of 12 and 19 nM, respectively. We observed that BDS-I and BDS-II have some sequence homologies with other sea anemone Na+ channels toxins, such as AsI, AsII, and AxI. However, they had a weak effect on tetrodotoxin-sensitive Na+ channels in neuroblastoma cells and no effect on Na+ channels in cardiac and skeletal muscle cells. BDS-I and BDS-II are the first specific blockers identified so far for the rapidly inactivating Kv3.4 channel.
Diochot
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S
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Schweitz
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H
Béress
L
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Lazdunski
M
M
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003064:Cnidarian Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007457:Iodine Radioisotopes; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers; D051381:Rats; D012615:Sea Anemones; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
C072544:BDS II protein, Anemonia sulcata; C059796:BDS-I antiviral protein, Anemonia sulcata; D003064:Cnidarian Venoms; D007457:Iodine Radioisotopes; D026902:Potassium Channel Blockers