SNX-482

SNX-482 is a toxin from the tarantula Hysterocrates gigas. It acts as a high-affinity blocker of R-type 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 of the spider Hysterocrates gigas.^[1]

Sequence

GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH^[1]

Homology

SNX-482 is homologous to the spider peptides grammatoxin S1A and hanatoxin.^[1]

Target

Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca²⁺ channel, P/Q type Ca²⁺ channel, Na⁺ channel.^[1]^[2]^[3] "SNX-482 [also] dramatically reduced the A-type potassium current in acutely dissociated dopamine neurons from mouse substantia nigra pars compacta."^[4]

Mode of action

The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels.

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.^[1] 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.^[2] SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating.^[2] 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.^[1]^[2]^[3]