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 scorpionCentruroides noxius, on the K currents of perfused squid giant axons using the voltage-clamp technique. At concentrations below 1.5 μM, NTX blocked K currents in a voltage-independent manner, with little effect on their turning-on and turning-off kinetics. Above 1.5 μM, the block by NTX became voltagedependent 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 μM 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 venomCentruroides 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.