Peptide toxins isolated from spider venom that modulate gating of voltage-dependent K+ channels

Abstract

Spider venom, like snake, bee and scorpion venom, is a rich source of ion channel modulators. Spider toxins that block Ca2+ channels and glutamate receptor-operated channels have been described. Recently, two new families of toxins that block K+ channels were isolated from spider venom. Hanatoxins, isolated from the venom of the Chilean tarantula Grammostola spatulata, inhibit Kv2.1 and Kv4.2. Kv2.1 is a Shab-related voltage activated K+ channel isolated from rat brain; Kv4.2 is a Shal-related K+ channel responsible for the transient outward K+ current (Ito) that initiates repolarization of cardiac and neural action potentials. Three toxins (heteropodotoxins) isolated from the venom of a free-living spider, Heteropoda venatoria, also inhibit Kv4.2. Because spider venom is logistically difficult to obtain, much less is known about spider venoms than snake and scorpion venoms. It is likely that development of this resource in reserve will yield many more interesting and useful ion channel modulators.