Blocking of the squid axon K+ channel by noxiustoxin: a toxin from the venom of the scorpionCentruroides noxius

Abstract

We have studied the selective effects of noxiustoxin (NTX), a fraction of the venom of the scorpion Centruroides noxius, on the K currents of perfused squid giant axons using the voltage-clamp technique. At concentrations below 1.5 microM, NTX blocked K currents in a voltage-independent manner, with little effect on their turning-on and turning-off kinetics. Above 1.5 microM, the block by NTX became voltage-dependent and could be partially removed by repetitive pulsing and strong depolarizations. Long repolarizations and more negative holding potentials favoured the slow restoration of channel block. Reduction of K currents by internally perfusing the fibers with solutions of low K+ concentration (200 mM), affected very little the removal of NTX-block during repetitive pulsing, suggesting that block removal depended on membrane potential and not on outward movements of K+ ions through open channels. In high extracellular K+ (300 mM) the blocking action of NTX was reduced and the instantaneous I-V characteristics showed a marked outward rectification. At 20 microM NTX, inward tail currents measured on step repolarizations to -70 mV were fully blocked, suggesting a direct interaction of the toxin with the open channel. The effects of the total venom Centruroides noxius Hoffmann was also studied. External application of 0.25 mg/ml of the venom caused a marked reduction of both Na and K currents, an effect similar to that of other scorpion venoms.

Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels.

“…ChTX was also compared with other known peptide inhibitors of K+ channels. A high level of similarity was detected between ChTX and noxiustoxin, a toxin from the venom of the scorpion Centuroides noxius that blocks the delayed rectifier K+ channel of the squid giant axon (20). The best alignment between ChTX and noxiustoxin (Fig.…”

Bradykinin-induced potassium current in cultured bovine aortic endothelial cells

“…However, two other compounds, TBA and NTX did inhibit the current. NTX has been shown to inhibit the maxi Ca2+-activated K + channel in membranes derived from transverse tubules of skeletal muscle incorporated into planar lipid bilayers with a Kd of 450 nM (Valdivia et al, 1988) and has also been shown to block the delayed rectifier current in squid axon (Carbone et al, 1982(Carbone et al, , 1987.…”

Pharmacology of K+ channels in the plasmalemma of the green algaChara corallina

“…Further analogies to channels in animal tissues may be found as more polypeptide toxins are characterized to be highly specific inhibitors of various K + channels (see recent work by Carbone et al, 1982Carbone et al, , 1987Lucero & Pappone, 1987). The possibility that these toxins could be used to help isolate the proteins could clearly lead to great advances in the study of these channel proteins.…”