Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle.

TLDR

The study used whole‑cell and unitary patch‑clamp recordings to examine how the 27‑residue peptide omega‑conotoxin GVIA blocks Ca²⁺ channels in various cell types. Omega‑conotoxin GVIA persistently blocks L‑ and N‑type Ca²⁺ channels in dorsal root ganglion, sympathetic, and hippocampal neurons, transiently inhibits T‑type channels, has no effect on cardiac, skeletal, or smooth muscle cells, acts directly on an external channel site without second‑messenger involvement, and its slow, reversible, neuron‑specific blockade makes it a valuable tool for isolating and studying neuronal Ca²⁺ channels.

Abstract

Blockade of Ca2+ channels by omega-conotoxin GVIA, a 27 amino acid peptide from the venom of the marine snail Conus geographus, was investigated with patch-clamp recordings of whole-cell and unitary currents in a variety of cell types. In dorsal root ganglion neurons, the toxin produces persistent block of L- and N-type Ca2+ channels but only transiently inhibits T-type channels. Its actions appear to be neuron-specific, since it blocks high-threshold Ca2+ channels in sensory, sympathetic, and hippocampal neurons of vertebrates but not in cardiac, skeletal, or smooth muscle cells. Block occurs through direct interaction of the toxin with an external site closely associated with the Ca2+ channel, without apparent involvement of a second messenger or dependence on channel gating. The tissue and channel-type specificity and the directness and slow reversibility of the block are features that favor use of omega-conotoxin as a tool for purifying particular neuronal Ca2+ channels and defining their physiological function.