Stromatoxin is a spider

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

that blocks certain delayed-rectifier and A-type

voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized ce ...

Etymology

Stromatoxin was first identified in the venom of the African

tarantula Tarantulas comprise a group of large and often hairy spiders of the family Theraphosidae. , 1,040 species have been identified, with 156 genera. The term "tarantula" is usually used to describe members of the family Theraphosidae, although ...

''Stromatopelma calceatum'' (the featherleg baboon spider), from which it derives its name. The technical abbreviation for the toxin is ScTx1.

Chemistry

Stromatoxin is a peptide consisting of 34 amino acids that belongs to the structural family of ‘

inhibitor cystine knot An inhibitor cystine knot (aka ICK or Knottin) is a protein structural motif containing three disulfide bridges. Knottins are one of three folds in the cystine knot motif; the other closely related knots are the Growth Factor Cystine Knot (GFCK) ...

’ spider peptides. The toxin was identified using a systematical screening of the effects of toxins of several species of tarantulas on Kv2-channels of ''

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

'' (the

African clawed frog The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

) .

Bioassay A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (''in vivo''), or on living cells or tissues(''in vitro''). A bioassay can be either quantal or quantitative, dir ...

guided fractionation and chromatography identified stromatoxin as the functional component. The full sequence of the venom was obtained in a single run of Edman sequencing and confirmed by mass spectrometry. The sequence of this toxin is ‘dctrmfgacr rdsdccphlg ckptskycaw dgti’, for an explanation of these symbols, see the

list of standard amino acids Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...

Target

Stromatoxin blocks the delayed-rectifier type potassium channels Kv2.1, Kv2.2, Kv2.1/9.3 and the A-type potassium channel Kv4.2, with affinity (IC₅₀) of 12.7 nM, 21.4 nM, 7.2 nM and 1.2 nM, respectively. No activity on Kv4.1 and Kv4.3 has been observed .

Mode of action

showed that the effect of stromatoxin on

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

is voltage-dependent, maximal inhibition is reached between –30 and 0 mV, while inhibition is only partial at values more positive than +10 mV. The toxin therefore acts as a gating modifier, shifting the activation of the channel to more depolarized potentials. Although the channel can still be activated, a much larger depolarization is needed. By blocking potassium channels, stromatoxin has a wide range of actions. Its target channels can be found in cardiac tissue, neurons and smooth muscle cells. In cardiac cells, their role more specifically concerns the height and duration of the plateau phase of the action potential, repolarization of cell membranes, cardiac refractoriness and automaticity. In the nervous system, A-type and delayed rectifier

s determine the membrane resting potential, the firing pattern, action potential duration and repolarization. Thus, they are implicated in membrane excitability, hormone release, and signal transduction and processing , , . The effect of the toxin strongly varies with the tissue in which the channels are expressed. Stromatoxin for example prohibits apoptosis in enterocytes and enhances myogenic constriction in (rat) cerebral arteries .

Toxicity

No toxic effects of stromatoxin have been recorded ''in vivo''. injected stromatoxin in mice, but observed no neurotoxicity.

References

. . . . . . {{Toxins Ion channel toxins Spider toxins