MicroO-conotoxin MrVIA inhibits mammalian sodium channels, but not through site I.
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.
Max-Planck-Institut für experimentelle Medizin, Göttingen, Germany.
H
H
Terlau
M
M
Stocker
K J
KJ
Shon
J M
JM
McIntosh
B M
BM
Olivera
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D020916:Conotoxins; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism; D004593:Electrophorus; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D009431:Neural Conduction / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012530:Saxitoxin / Q000378:metabolism / Q000494:pharmacology; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism / Q000494:pharmacology; D014982:Xenopus laevis / Q000378:metabolism
D020916:Conotoxins; D010455:Peptides; D015222:Sodium Channels; C093338:conotoxin MrVIA; D012530:Saxitoxin; D013779:Tetrodotoxin