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Neuronal expression of an FMRFamide-gated Na+ channel and its modulation by acid pH

By S.J. Perry, Volko A. Straub, M.G. Schofield, J.F. Burke and P.R. Benjamin


The molluscan Phe-Met-Arg-Phe-amide (FMRFamide)-gated sodium channels (FaNaCs) show both structural and functional similarities to the mammalian acid-sensing ion channels (ASICs). Both channel types are related to the epithelial sodium channels and, although the neuropeptide FMRFamide directly gates the FaNaCs, it also modulates the proton-gating properties of ASICs. It is not yet known whether protons can alter the gating properties of the FaNaCs. We chose to examine this possibility at a site of FaNaC expression in the nervous system of the mollusk Lymnaea stagnalis. We cloned a putative L. stagnalis FaNaC (LsFaNaC) that exhibited a high degree of sequence identity to the Helix aspersa FaNaC (HaFaNaC, 60%), and a weaker homology to the ASICs (ASIC3, 22%). In situ hybridization was used to map the LsFaNaC expression pattern in the brain and to identify the right pedal giant1 (RPeD1) neuron as a site where the properties of the endogenous channel could be studied. In RPeD1 neurons isolated in culture, we demonstrated the presence of an FMRFamide-gated sodium current with features expected for a FaNaC: amiloride sensitivity, sodium selectivity, specificity for FMRFamide and Phe-Leu-Arg-Phe-amide (FLRFamide), and no dependency on G-protein coupling. The sodium current also exhibited rapid desensitization in response to repeated FMRFamide applications. Lowering of the pH of the bathing solution reduced the amplitude of the FMRFamide-gated inward current, while also activating an additional sustained weak inward current that was apparently not mediated by the FaNaC. Acidification also prevented the desensitization of the FMRFamide-induced inward current. The acid sensitivity of LsFaNaC is consistent with the hypothesis that FaNaCs share a common ancestry with the ASICsPeer reviewedPublisher versio

Publisher: Society for Neuroscience
Year: 2001
OAI identifier:

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  1. (1989). A comparison of 4 techniques for mapping the distribution of serotonin and serotonincontaining neurons in fixed and living ganglia of the snail, doi
  2. (1993). A molecularly defined cardiorespiratory interneuron expressing SDPFLRFamide/GDPFLRFamide in the snail Lymnaea: monosynaptic connections and pharmacology.
  3. (1997). A proton-gated cation channel involved in acid-sensing. doi
  4. (1998). A sensory neuronspecific, proton-gated ion channel. doi
  5. (1997). BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. doi
  6. (2000). Cloning and expression of a FMRFamide-gated Na 1 channel from Helisoma trivolvis and comparison with the native neuronal channel. doi
  7. (1995). Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium-channel. doi
  8. (1999). Cyclic AMP is involved in cardioregulation by multiple neuropeptides encoded on the FMRFamide gene.
  9. (1998). Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. doi
  10. (1978). FMRFamide increases the adenylate cyclase activity and cyclic AMP level of molluscan heart. doi
  11. (2001). FMRFamide-Gated Na1 Channel and Its Modulation by Acid pH
  12. (2001). FMRFamide-Gated Na1 Channel and Its Modulation by Acid pH cology of the myogenic heart of the pond snail Lymnaea stagnalis.
  13. (1998). H 1-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. doi
  14. (1982). Immuno-cytochemical demonstration of peptidergic cells in the pond snail Lymnaea stagnalis with an antiserum to the molluscan cardioactive tetrapeptide FMRFamide. doi
  15. (1990). In vitro reconstruction of the respiratory central pattern generator of the mollusk Lymnaea. doi
  16. (1992). Influence of extracellular and intracellular pH on GABA-gated chloride conductance in grayfish muscle fibres. doi
  17. (1999). Inositol-1,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate are second messenger targets for cardioactive neuropeptides encoded on the FMRFamide gene.
  18. (1992). Ionic channels of excitable membranes, doi
  19. (1988). Isolation, characterization, and evolutionary aspects of a cDNA clone encoding multiple neuropeptides involved in the stereotyped egg-laying behavior of the fresh water snail Lymnaea stagnalis.
  20. (1985). Isolation, sequencing, synthesis, and pharmacological characterization of 2 brain neuropeptides that modulate the action of morphine. doi
  21. (1987). Lipoxygenase metabolites of arachidonic acid as 2nd messengers for presynaptic inhibition of Aplysia sensory cells. doi
  22. (2001). Modulation by extracellular pH of low- and high-voltage-activated calcium currents of rat thalamic relay neurons.
  23. (1997). Molecular cloning of a non-inactivating protongated Na 1 channel specific for sensory neurons. doi
  24. (1996). Myomodulin gene of Lymnaea: structure, expression, and analysis of neuropeptides.
  25. (1991). Nerve growth factor (NGF) induces sprouting of specific neurons of the snail, doi
  26. (1998). pH modulation of ligand-gated ion channels. In: pH and brain function
  27. PR (1990b) Regulation of heartbeat in Lymnaea by motoneurons containing FMRFamide-like peptides.
  28. (1995). Properties of an identified dopaminecontaining neurone in culture from the snail Helisoma. Exp Physiol 80:37–51. doi
  29. (2000). Structure-activity studies on the Helix FMRFamide-gated sodium channel. Soc Neurosci Abstr 26:917.
  30. (1980). Synaptic relationships of the cerebral giant cells with motoneurons in the feeding system of Lymnaea stagnalis.
  31. (1987). The brain of Lymnaea contains a family of FMRFamide-like peptides. doi
  32. (2001). The effects of pH on the interaction between capsaicin and the vanilloid receptor in rat dorsal root ganglia neurons. doi
  33. (1997). The first peptide-gated ion channel.
  34. (1981). The neuronal organization of the paired pedal ganglia of Lymnaea stagnalis (L). Comp Biochem Physiol [A] doi
  35. (1985). The neuropeptide FMRFamide decreases both the Ca 21 conductance and a cyclic 39,59-adenosine monophosphate-dependent K 1 conductance in identified molluscan neurons.
  36. (1998). The Phe-MetArg-Phe-amide-activated sodium channel is a tetramer. doi
  37. (1987). The variety and distribution of FMRFamide-related peptides in mollusks.

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