Homologues of a K(+) channel blocker ?-dendrotoxin: characterization of synaptosomal binding sites and their coupling to elevation of cytosolic free calcium concentration.

Three polypeptides (?, ? and ?) homologous to ?-dendrotoxin, an inhibitor of certain voltage-activated K(+) channels, were found to elevate the cytosolic free concentration of calcium ([Ca(2+)](c)) in isolated central nerve terminals. Relative to ?-dendrotoxin (EC(50) ? 2.1 nM), the ?-, ?- and ?-toxins were 790-, 214- and 5.7-fold less effective; no additivity was apparent in the toxins' effects on [Ca(2+)](c). Each toxin antagonized the high affinity binding of (125)I-labelled ?- and ?-dendrotoxin to synaptosomes but with different potencies. The mutual interaction of ?- and ?-dendrotoxin with the acceptor appeared complex, the inhibition curves being noticeably extended. For the inhibition of binding of ?- and ?-dendrotoxin, the respective K(i)'s (nM) observed for ?, ?, ? and ? toxins were 0.78, 50, 99, 8, and 2.3, 95, 61, 0.53. Apparently, interactions of ?- and ?-, but not ?- or ?-dendrotoxin with the acceptor are closely coupled to an inhibition of K(+) channel(s) as observed indirectly by elevation of [Ca(2+)](c).