Charybdotoxin

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Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.

Contents

[edit] Chemical properties

Scorpions such as the deathstalker paralyse their prey by injecting a potent mix of peptide toxins[1]. Charybdotoxin (CTX), a 37 amino acid neurotoxin, is one of the peptide toxins that can be extracted from the venom of the scorpion. Its structure is very similar to that of margatoxin. Charybdotoxin contains three disulfide bridges[2].

[edit] Mode of action

Charybdotoxin occludes the pore of calcium-activated voltage-gated K+ channels by binding to one of four independent, overlapping binding sites[3][4]. It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered[5]. The blockade of K+ channels by the charybdotoxin peptide causes neuronal hyperexcitability.

[edit] Treatment

Anti-scorpion venom serum (AScVS) is an effective and safe method of therapy in severe scorpion envenoming syndrome. Compared with other therapies like alpha blockers it has a relatively short recovery period (10 vs 16-42 hours)[6].

[edit] References

  1. ^ Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, Williams SM. Neuroscience, p82.
  2. ^ Avdonin V, Nolan B, Sabatier JM, Waard M de, Hoshi T, Mechanisms of Maurotoxin Action on Shaker Potassium Channels, Biophys J. 2000 August; 79: 776–787. [1]
  3. ^ Thompson J, Begenisich T, Electrostatic interaction between charbotoxin and a tetrameric mutant of Shaker K+ channels, Biophys J. 2000 May; 78(5): 2382-91. [2]
  4. ^ Naranjo D, Miller C, A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel, Neuron. 1996 Jan; 16(1): 123-30. [3]
  5. ^ MacKinnon R, Reinhart PH, White MM, Charybdotoxin block of Shaker K+ channels suggests that different types of K+ channels share common structural features. Dec. 1988; 1 (10) 997-1001. [4]
  6. ^ Natu VS, Murthy RK, Deodhar KP, Efficacy of species specific anti-scorpion venom serum (ASvVS) agains severe, serious scorpion stings – an experience from rural hospital in western Maharashtra, J. Assoc Physicians India. 2006 Apr;54:283-7. [5]
  • Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. New York: McGraw-Hill 2000, p158.</ref>
  • Sunderland: Sinauer Associates Sutherland ML, Williams SH, Abedi R, Overbeek PA, Pfaffinger PJ, Noebels JL, Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression, PNAS 1999 March; 96(5): 2451-55. [6]</ref>
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