Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel

Abstract

THE peptide Phe-Met-Arg-Phe-NH₂ (FMRFamide) and structurally related peptides are present both in invertebrate and vertebrate nervous systems^1,2. Although they constitute a major class of invertebrate peptide neurotransmitters³, the molecular structure of their receptors has not yet been identified. In neurons of the snail Helix aspersa⁴, as well as in Aplysia bursting⁵ and motor⁶ neurons, FMRFamide induces a fast excitatory depolarizing response due to direct activation of an amiloride-sensitive Na⁺ channel⁴. We have now isolated a complementary DNA from Helix nervous tissue; when expressed in Xenopus oocytes, it encodes an FMRF-amide-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^7–12 and Caenorhabditis elegans degenerins^13–15, but it displays the same overall structural organization. To our knowledge, this is the first characterization of a peptide-gated ionotropic receptor.