Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel.
The peptide Phe-Met-Arg-Phe-NH2 (FMRFamide) and structurally related peptides are present both in invertebrate and vertebrate nervous systems. Although they constitute a major class of invertebrate peptide neurotransmitters, the molecular structure of their receptors has not yet been identified. In neurons of the snail Helix aspersa, as well as in Aplysia bursting and motor neurons, FMRFamide induces a fast excitatory depolarizing response due to direct activation of an amiloride-sensitive Na+ channel. We have now isolated a complementary DNA from Helix nervous tissue; when expressed in Xenopus oocytes, it encodes an FMRFamide-activated Na+ channel (FaNaCh) that can be blocked by amiloride. The corresponding protein shares a very low sequence identity with the previously cloned epithelial Na+ channel subunits and Caenorhabditis elegans degenerins, but it displays the same overall structural organization. To our knowledge, this is the first characterization of a peptide-gated ionotropic receptor.
Lingueglia
E
E
Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Valbonne, France.
Champigny
G
G
Lazdunski
M
M
Barbry
P
P
D000584:Amiloride / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D019835:FMRFamide; D006372:Helix, Snails; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics*; D014981:Xenopus
D018076:DNA, Complementary; C097095:FaNaCh protein, Helix aspersa; D009479:Neuropeptides; D011994:Recombinant Proteins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019835:FMRFamide; D000584:Amiloride