J Neurophysiol 1996 Sep 01;763:1423-9. doi: 10.1152/jn.1996.76.3.1423.

MicroO-conotoxin MrVIA inhibits mammalian sodium channels, but not through site I.

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1. A 31-amino-acid peptide from the venom of the snail-hunting species Conus marmoreus, microO-conotoxin MrVIA, inhibits mammalian voltage-gated sodium channels through a novel mechanism distinct from saxitoxin, tetrodotoxin, or mu-conotoxin. 2. MicroO-Conotoxin MrVIA blocks rat brain type II sodium channels expressed in Xenopus oocytes (IC50 approximately 200 nM, Hill coefficient approximately 1.6 +/- 0.2, mean +/- SE). Channel activation/inactivation kinetics and current-voltage relationships were unperturbed. 3. MicroO-Conotoxin MrVIA does not cause phasic or use-dependent inhibition of sodium currents measured in Xenopus oocytes expressing rat brain type II sodium channels, but shifts the steady-state availability of these sodium channels to more hyperpolarized potentials. 4. MicroO-Conotoxin MrVIA inhibited rapidly inactivating sodium channel conductance in rat hippocampal cells in culture. The inhibition was rapidly reversible. 5. MicroO-Conotoxin MrVIA does not displace specific [3H]saxitoxin binding to either rat brain or Electrophorus electric organ sites, indicating inhibitory effects mediated through a binding site distinct from site I.

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Species referenced: Xenopus laevis
Genes referenced: snai1