Sea anemone Bartholomea annulata venom inhibits voltage-gated Na + channels and activates GABA A receptors from mammals

Toxin production in nematocysts by Cnidaria phylum represents an important source of bioactive compounds. Using electrophysiology and, heterologous expression of mammalian ion channels in the Xenopus oocyte membrane, we identified two main effects produced by the sea anemone Bartholomea annulata venom. Nematocysts isolation and controlled discharge of their content, revealed that venom had potent effects on both voltage-dependent Na + (Na v ) channels and GABA type A channel receptors (GABA A R), two essential proteins in central nervous system signaling. Unlike many others sea anemone toxins, which slow the inactivation rate of Na v channels, B. annulata venom potently inhibited the neuronal action potential and the Na + currents generated by distinct Na v channels opening, including human TTX-sensitive (hNa v 1.6) and TTX-insensitive Na v channels (hNa v 1.5). A second effect of B. annulata venom was an agonistic action on GABA A R that activated distinct receptors conformed by either α1β2γ2, α3β2γ1 or, ρ1 homomeric receptors. Since GABA was detected in venom samples by ELISA assay at low nanomolar range, it was excluded that GABA from nematocysts directly activated the GABA A Rs. This revealed that substances in B. annulata nematocysts generated at least two potent and novel effects on mammalian ion channels that are crucial for nervous system signaling.