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J Neurophysiol 76: 1423-1429, 1996;
0022-3077/96 $5.00
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Journal of Neurophysiology, Vol 76, Issue 3 1423-1429, Copyright © 1996 by APS

ARTICLES

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

H. Terlau, M. Stocker, K. J. Shon, J. M. McIntosh and B. M. Olivera
Max-Planck-Institut fur experimentelle Medizin, Gottingen, Germany.

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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