Charybdotoxin, a protein inhibitor of single Ca²⁺-activated K⁺ channels from mammalian skeletal muscle

Abstract

The recent development of techniques for recording currents through single ionic channels¹ has led to the identification of a K⁺-specific channel that is activated by cytoplasmic Ca²⁺ (refs 2–12). The channel has complex properties, being activated by depolarizing voltages and having a voltage-sensitivity that is modulated by cytoplasmic Ca²⁺ levels. The conduction behaviour of the channel is also unusual, its high ionic selectivity being displayed simultaneously with a very high unitary conductance^2,4,12. Very little is known about the biochemistry of this channel, largely due to the lack of a suitable ligand for use as a biochemical probe for the channel. We describe here a protein inhibitor of single Ca²⁺-activated K⁺ channels of mammalian skeletal muscle. This inhibitor, a minor component of the venom of the Israeli scorpion, Leiurus quinquestriatus, reversibly blocks the large Ca²⁺-activated K⁺ channel in a simple bimolecular reaction. We have partially purified the active component, a basic protein of relative molecular mass (M_r) ∼ 7,000.