Potassium channel blockade by the B subunit of beta-bungarotoxin.

beta-Bungarotoxin (beta-BTX) isolated from the venom of Bungarus multicinctus has previously been reported to be a neurotoxic protein. The toxin is composed of two subunit chains, denoted A and B. The intact toxin was first examined in this study for its ability to block central nerve ending K channels using the 86Rb efflux technique. beta-BTX, when preincubated with synaptosomes for 30 min in the absence of extracellular Ca2+, selectively inhibited the slowly inactivating voltage-dependent (S) component of 86Rb efflux. The EC50 for inhibition is 1 to 3 nM. The two subunit chains were separated and isolated by reduction and carboxymethylation of the parent toxin. The K channel-blocking activity was associated only with the reduced and carboxymethylated B-subunit of beta-BTX (RCM-B). The dose-dependent inhibition by RCM-B exhibited an apparent biphasic response, with the noninactivating voltage-gated K channel being more susceptible to RCM-B inhibition (EC50 = 0.1 to 0.3 nM) than to inhibition by the parent compound. Additionally, the inactivating voltage-gated K channel (T) was sensitive to inhibition by higher concentrations of RCM-B (EC50 = 1 to 3 nM). These results suggest that the B-chain of beta-BTX may be responsible for blockade of certain voltage-gated K channels in a manner that is not directly related to the known phospholipase activity of the intact molecule.