H. Terlau et al., MU-O-CONOTOXIN MRVIA INHIBITS MAMMALIAN SODIUM-CHANNELS, BUT NOT THROUGH SITE-I, Journal of neurophysiology, 76(3), 1996, pp. 1423-1429
1. A 31-amino-acid peptide from the venom of the snail-hunting species
Conus marmoreus, mu O-conotoxin MrVIA, inhibits mammalian voltage-gat
ed sodium channels through a novel mechanism distinct from saxitoxin,
tetrodotoxin, or mu-conotoxin. 2. mu O-Conotoxin MrVIA blocks rat brai
n type II sodium channels expressed in Xenopus oocytes (IC50 similar t
o 200 nhl, Hill coefficient similar to 1.6 +/- 0.2, mean +/- SE). Chan
nel activation/inactivation kinetics and current-voltage relationships
were unperturbed. 3. mu O-Conotoxin MrVIA does not cause phasic or us
e-dependent inhibition of sodium currents measured in Xenopus oocytes
expressing rat brain type II sodium channels, but shifts the steady-st
ate availability of these sodium channels to more hyperpolarized poten
tials. 4. mu O-Conotoxin MrVIA inhibited rapidly inactivating sodium c
hannel conductance in rat hippocampal cells in culture. The inhibition
was rapidly reversible. 5. mu O-Conotoxin MrVIA does not displace spe
cific [H-3]saxitoxin binding to either rat brain or Electrophorus elec
tric organ sites, indicating inhibitory effects mediated through a bin
ding site distinct from site I.