Selective blockage of voltage-dependent K+ channels by a novel scorpion toxin

Blocking agents of high selectivity are crucial in defining both physiologically and biochemically the molecular components that control membrane excitability. To obtain such probes for voltage-dependent ion channels, we have examined the venom of several American scorpions for the presence of polypeptide neurotoxins having the required properties. We report here that using voltage-clamped giant axons of the squid Loligo vulgaris we have identified in the venom of the scorpion Centruroides noxius Hoffmann a polypeptide (fraction II-11) that specifically depresses the peak permeability of K⁺ channels without affecting their voltage-dependent open-close kinetics. The venom also contains a polypeptide toxin (fraction II-10) that specifically depresses Na⁺ peak permeability with only minor effects on the activation-inactivation kinetics. Furthermore, the physiological effects of the whole venom on the squid giant axon can be assigned quantitatively to the combined action of the two polypeptides.