(full paper is archived in the Miller Library)
Title: Effects of Conus striatus venom on voltage-gated K+ channels in frog sympathetic ganglia neurons
Student Author(s): Etchebarne, Brett E.
Faculty Advisor(s): Gilly, William
Location: Final Papers Biology 176H
Date: June 2001
Abstract: Cone snails are predatory marine gastropods of the genus Conus which proliferated to over 500 species world wide largely through the use of novel peptide toxins (conotoxins) that are injected into prey items through a harpooning apparatus. Conotoxins have evolved for maximal effect on prey species hunted by each cone snail species (Duda and Palumbi 1999). All cone snail venoms examined thus far contain peptides that act with great specificity on a variety of channels including K+, Na+, Ca2+, and ACh receptors (Olivera et al. 1999).
Conus striatus is a fish-hunting snail indigenous to the Indo-Pacific region. Venom samples were "milked" from the snails and were further diluted during experiments. Voltage-dependent K+ currents were recorded from frog sympathetic ganglia (SG) neurons using the whole-cell patch-clamp technique. When applied to the bathing solution, the venom was found to induce a reduction in IK during a voltage step. This reduction was evident at venom dilution levels equivalent approximately eight times higher than those shown to elicit repetitive action potentials in frog nerve-muscle preparations (Schulz and Gilly, unpublished results). It is thus possible that the block of voltage-gated K+ channels in frog SG neurons by the venom component may be involved in this neuroexcitatory activity.
Further studies have shown that IK in these cells was found to be insensitive to externally applied S-nitrosodithiothreitol (SNDTT), a compound that shows a high degree of specificity for block of the Kv1 subfamily (Brock, Mathes, and Gilly, 1997). Additionally, the venom-sensitive current was found to overlap with that blocked by externally applied tetraethylammonium (TEA), which has been shown to selectively inhibit delayed rectifier (DR) IK in frog SG neurons (Spruce et al., 1987 and Klemic, et al., 1998).
Together, these results suggest the existence of a previously undescribed blocker of DR IK in C. striatus venom which functions in a manner most similar to snake-derived dendrotoxins in frog peripheral neurons (Anderson and Harvey, 1985) and is not targeting Kv1-type channels.