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

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journal contribution
posted on 08.12.2009, 16:11 by S.J. Perry, Volko A. Straub, M.G. Schofield, J.F. Burke, 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 ASICs



Journal of Neuroscience, 2001, 21 (15), pp.5559-5567


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