Modulation of insect Ca(v) channels by peptidic spider toxins

Insects have a much smaller repertoire of voltage-gated calcium (Ca(V)) channels than vertebrates. Drosophila melanogaster harbors only a single ortholog of each of the vertebrate Ca(V)1, Ca(V)2, and Ca(V)3 subtypes, although its basal inventory is expanded by alternative splicing and editing of Ca(V) channel transcripts. Nevertheless, there appears to be little functional plasticity within this limited panel of insect Ca(V) channels, since severe loss-of-function mutations in genes encoding the pore-forming alpha1 subunits in Drosophila are embryonic lethal. Since the primary role of spider venom is to paralyze or kill insect prey, it is not surprising that most, if not all, spider venoms contain peptides that potently modify the activity of these functionally critical insect Ca(V) channels. Unfortunately, it has proven difficult to determine the precise ion channel subtypes recognized by these peptide toxins since insect Ca(V) channels have significantly different pharmacology to their vertebrate counterparts, and cloned insect Ca(V) channels are not available for electrophysiological studies. However, biochemical and genetic studies indicate that some of these spider toxins might ultimately become the defining pharmacology for certain subtypes of insect Ca(V) channels. This review focuses on peptidic spider toxins that specifically target insect Ca(V) channels. In addition to providing novel molecular tools for ion channel characterization, some of these toxins are being used as leads to develop new methods for controlling insect pests.