Neuronal Expression of an FMRFAmide-Gated Sodium Channel and its Modulation by Acid pH

Perry, Stephen J, Straub, Volko A, Schofield, Michael G, Burke, Julian F and Benjamin, Paul R (2001) Neuronal Expression of an FMRFAmide-Gated Sodium Channel and its Modulation by Acid pH. Journal of Neuroscience, 21 (15). pp. 5559-5567. ISSN 0270-6474

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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.

Item Type: Article
Additional Information: The first two authors were postdoctoral RAs on this project funded by my grant. The third author was my technician. I was the electrophysiologist on this multidisciplinary project and contributed 50% to the intellectual input to this paper and 70% to its writing.
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Michael Schofield
Date Deposited: 06 Feb 2012 20:07
Last Modified: 26 Mar 2012 08:16
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