Spider toxins: A new group of potassium channel modulators

Spider toxins that target potassium channels constitute a new class of phar macological tools that can be used to probe the structure and function of t hese channels at the molecular level. The limited studies performed to date indicate that these peptide toxins may facilitate the analysis of K+ chann els that have proved insensitive to peptide inhibitors isolated from other animal sources. Thus far, two classes of K+ channel-selective spider toxins have been isolated, sequenced, and pharmacologically characterised - the h anatoxins (HaTx) from Grammastola spatulata and heteropodatoxins (HpTx) fro m Heteropoda venatoria. The hanatoxins block Kv2.1 and Kv4.2 voltage-gated K+ channels. In Kv2.1 K+ channels this occurs as a consequence of a depolar ising shift in the voltage dependence of activation and not by occlusion of the channel pore. These toxins show minimal sequence homology with other p eptide inhibitors of K+ channels, but they do share some homology with othe r ion channel toxins from spiders, particularly with regard to the spacing between cysteine residues. We have recently isolated three K+ channel antag onists from the venom of the Australian funnel-web spider Hadronyche versut a; at least two of these toxins are likely to constitute a new class of spi der toxins active on K+ channels as they are approximately twice as large a s HaTx and HpTx.