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How the toxin Vc1.1 (snail venom) inhibits neuronal calcium channels to reduce neuropathic pain

The venom from marine cone snails, used to immobilize prey, contains numerous peptides called conotoxins, some of which can act as painkillers in mammals. A recent study in provides new insight into the mechanisms by which one conotoxin, Vc1.1, inhibits pain. The findings help explain the analgesic powers of this naturally occurring toxin and could eventually lead to the development of synthetic forms of Vc1.1 to treat certain types of in humans.

Neuropathic pain, a form of that occurs in conjunction with injury to – or dysfunction of – the nervous system, can be debilitating and difficult to treat, and the medical community is eager to find better methods to minimize what can be a serious condition. Neuropathic pain is associated with changes in the transmission of signals between neurons, a process that depends on several types of voltage-gated (VGCCs). However, given the importance of these VGCCs in mediating normal neurotransmission, using them as a pharmacological target against neuropathic pain could potentially lead to undesirable side effects.

In previous studies, and colleagues from RMIT University in Melbourne showed that Vc1.1 acted against neuropathic pain in mice; they found that, rather than acting directly to block VGCCs, Vc1.1 acts through GABA type B (GABAB) receptors to inhibit N-type (Cav2.2) channels.

Now, Adams and colleagues show that Vc1.1 also acts through GABAB receptors to inhibit a second, mysterious class of neuronal VGCCs that have been implicated in pain signaling but have not been well understood – R-type (Cav2.3) channels. Their new findings not only help solve the mystery of Cav2.3 function, but identify them as targets for analgesic conotoxins.

Source

Article: Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and ?-conotoxin Vc1.1 via GABAB receptor activation Berecki, G., et al. 2014. J. Gen. Physiol. doi: 10.1085/jgp.201311104

Commentary: Rittenhouse, A.R. 2014. J. Gen. Physiol. 10.1085.jgp.201411190

Rockefeller University Press