SNX-482 is a toxin from the tarantula '' Hysterocrates gigas''. It acts as a high-affinity blocker of

R-type is a scrolling shooter, horizontally scrolling shooter arcade video game developed and released by Irem in 1987 and the first game in the List of R-Type video games, ''R-Type'' series. The player controls a star ship, the R-9 "Arrowhead", in ...

Ca²⁺ (Cav2.3) channels, but at higher concentrations it can also block other Ca²⁺ channels and Na⁺ channels.

Sources

SNX-482 is isolated from the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a ...

of the spider '' Hysterocrates gigas''.Robert Newcomb, et al., ''Biochemistry'' 1998, 37, 15353–15362

Sequence

GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH

Homology

SNX-482 is homologous to the spider peptides grammatoxin S1A and hanatoxin.

Target

Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca²⁺ channel, P/Q type Ca²⁺ channel, Na⁺ channel.Emmanuel Bourinet, et al., ''Biophysical Journal'', Volume 81, July 2001 79–88G Arroyo, et al., ''Eur J Pharmacol'', 2003, 475: 11–8

Mode of action

The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels. SNX-482 inhibits native R-type Ca²⁺ currents at weak

nanomolar Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...

concentrations in rat neurohypophyseal nerve terminals. However, it does not influence R-type Ca²⁺ currents at concentrations of 200–500 nM in several types of rat central neurons. Washout could only moderately reverse the R-type Ca²⁺ channel inhibition after treatment with 200 nM SNX-482. However, application of strong voltage reverses the blocking of R-type Ca²⁺ channels. SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating. Although SNX-482 is generally viewed as a selective inhibitor of Cav2.3 (a1E, R-type) channels, more recently it was shown that it can also inhibit L-type or P/Q type Ca²⁺ channels and incompletely block Na⁺ channels.

Research and therapeutic use

SNX-482 has been used to elucidate the roles of theaflavin-3-G in

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release. Furthermore, some research has indicated that it inhibits neuronal responses in a

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli ( allodynia). It may have continuo ...

model, so it is possible that SNX-482 can be used to reduce dorsal horn neuronal pain in

therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many differe ...

.Elizabeth A, et al., ''European Journal of Neuroscience'', Vol. 25, pp. 3561–3569, 2007

References

{{Reflist Ion channel toxins Neurotoxins