The microI skeletal muscle sodium channel: mutation E403Q eliminates sensitivity to tetrodotoxin but not to mu-conotoxins GIIIA and GIIIB.
Voltage-sensitive Na channels from nerve and muscle are blocked by the guanidinium toxins tetrodotoxin (TTX) and saxitoxin (STX). Mutagenesis studies of brain RII channels have shown that glutamate 387 (E387) is essential for current block by these toxins. We demonstrate here that mutation of glutamate 403 (E403) of the adult skeletal muscle microI channel (corresponding to E387 of RII) also prevents current blockade by TTX and STX, and by neo-saxitoxin. However, the mutation fails to prevent blockade by the peptide neurotoxins, mu-conotoxin GIIIA and GIIIB; these toxins are thought to bind to the same or overlapping sites with TTX and STX. The E403Q mutation may have utility as a marker for exogenous Na channels in transgenic expression studies, since there are no known native channels with the same pharmacological profile.
Stephan
M M
MM
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Potts
J F
JF
Agnew
W S
WS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D020916:Conotoxins; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018698:Glutamic Acid; D005973:Glutamine / Q000494:pharmacology; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry / Q000502:physiology*; D009154:Mutation; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D012530:Saxitoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D015222:Sodium Channels / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014982:Xenopus laevis
D020916:Conotoxins; D005971:Glutamates; D009466:Neuromuscular Blocking Agents; D010456:Peptides, Cyclic; D015222:Sodium Channels; D005973:Glutamine; C046101:conotoxin GIII; D012530:Saxitoxin; D018698:Glutamic Acid; D013779:Tetrodotoxin; C034902:neosaxitoxin; D004247:DNA