lysine residues in the β-turn region has provided more confounding results, appearing to be biologically critical in some dendrotoxin homologues and not necessary for others. Furthermore, mutation of the entire lysine triplet (K28-K29-K30) to Ala-Ala-Gly in alpha-DTX resulted in very little change in biological activity. There is a general agreement that the conserved lysine residue near the N-terminus (Lys5 in alpha-DTX) is crucial for the biological activity of all dendrotoxins, while additional residues, such as those in the beta-turn region, might play a role in dendrotoxin specificity by mediating the interactions of individual toxins to their individual target sites. This not only helps explain the stringent specificity of some dendrotoxins for different subtypes of voltage-gated K+ channels, but also accounts for differences in the potency of dendrotoxins for common K+ channels. For example, Wang et al. showed that the interaction of dendrotoxin-K with KV1.1 is mediated by its lysine residues in both the N-terminus and the β-turn region, while alpha-dendrotoxin appears to interact with its target solely through the N-terminus. This less expansive interactive domain may help explain why alpha-dendrotoxin is less discriminative while dendrotoxin-K is strictly selective for KV1.1. Uses in research Potassium channels of vertebrate neurons display a high degree of diversity that allows neurons to precisely tune their electrical signaling properties by expression of different combinations of potassium channel subunits. Furthermore, because they regulate ionic flux across biological membranes, they are important in many aspects of cellular regulation and signal transduction of different cell types. Therefore, voltage-gated potassium channels are targets for a wide range of potent biological toxins from such organisms as snakes, scorpions, sea anemones, and cone snails. Thus, venom purification has led to the isolation of peptide toxins such as the dendrotoxins, which have become useful pharmacological tools for the study of potassium channels. Because of their potency and selectivity for different subtypes of potassium channels, dendrotoxins have become useful as molecular probes for the structural and functional study of these proteins. This may help improve our understanding of the roles played by individual channel types, as well as assist in the pharmacological classification of these diverse channel types. Furthermore, the availability of radiolabelled dendrotoxins provides a tool for the screening of other sources in a search for new potassium channel toxins, such as the kalicludine class of potassium channel toxins in sea anemones. Lastly, the structural information provided by dendrotoxins may provide clues