Is acetylcholine a fast inhibitor? A family of genes encodes acetylcholine-gated chloride channels in C. elegans. Export

@inproceedings{citeulike:3321897, abstract = {Most fast cholinergic neurotransmission that people think about is excitatory and is mediated by cation-selective nicotinic acetylcholine receptors. However, molluscs also have fast inhibitory cholinergic neurotransmission (Kehoe et al., 1971) although channels mediating this mode of neurotransmission have never been cloned. We have shown that C. elegans encodes a family of ligand-gated ion channel subunits that form anion selective acetylcholine-gated channels when expressed in Xenopus oocytes (Putrenko et al., 2005). We have designated these subunits ACC-1 through 4. ACC-1 (F58G6.4) and ACC-2 (C53D6.3) each form acetylcholine sensitive homomers that are chloride, but not sodium or potassium permeable. They show no significant response to other neurotransmitters. They are potently blocked by the nicotinic antagonist d-tubocurarine but not strongly activated by the agonist nicotine. Arecoline is an effective agonist but with low affinity. The other two subunits ACC-3 (F55D10.5) and ACC-4 (T27E9.9) do not form ligand-responsive homomers but appear to form heteromeric channels with ACC-1 or ACC-2. In phylogenetic analyses, the ACC subunits, along with four other predicted subunit genes (K10D6.1, C50B6.11, F47A4.1 and Y71D11A.5), form a clade. We predict that these eight genes encode a family of acetylcholine-gated chloride channel subunits, which is most closely related to the serotonin-gated chloride channel subunit MOD-1. We are currently trying to determine the function of these channels. ACC-1 and 2 promoter::GFP fusions are expressed in apparently non-overlapping subsets of ring neurons and ACC-1 is expressed in the pair of M3 neurons in the pharynx whereas ACC-2 is expressed in enteric muscles. We have generated transgenic worms expressing RNAi hairpin constructs for ACC-1 and 2 driven by the endogenous promoters and are analyzing the effects of reduced ACC-1 and 2 expression in behavioral assays. (Kehoe, J., 1972, J. Physiol. 225, 85-114; Putrenko et al., 2005, J. Biol. Chem. 280, 6392-6398)}, author = {Putrenko, Igor and Zakikhani, Mahvash and Dent, Joseph A.}, citeulike-article-id = {3321897}, citeulike-linkout-0 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00026296}, journal = {International Worm Meeting}, keywords = {acc-1, acc-2, acc-3, acc-4, c50b611, c53d63, c\_elegans, caenorhabditis\_elegans, celegans, elegans, f47a41, f55d105, f58g64, k10d61, lgc-46, lgc-47, lgc-48, lgc-49, meeting\_abstract, nematode, t27e99, wormbase, y71d11a5}, posted-at = {2008-09-23 15:04:24}, priority = {3}, title = {Is acetylcholine a fast inhibitor? A family of genes encodes acetylcholine-gated chloride channels in C. elegans.}, url = {http://www.wormbase.org/db/misc/paper?name=WBPaper00026296}, year = {2005} }

TY - CONF ID - citeulike:3321897 L3 - citeulike-article-id:3321897 N2 - Most fast cholinergic neurotransmission that people think about is excitatory and is mediated by cation-selective nicotinic acetylcholine receptors. However, molluscs also have fast inhibitory cholinergic neurotransmission (Kehoe et al., 1971) although channels mediating this mode of neurotransmission have never been cloned. We have shown that C. elegans encodes a family of ligand-gated ion channel subunits that form anion selective acetylcholine-gated channels when expressed in Xenopus oocytes (Putrenko et al., 2005). We have designated these subunits ACC-1 through 4. ACC-1 (F58G6.4) and ACC-2 (C53D6.3) each form acetylcholine sensitive homomers that are chloride, but not sodium or potassium permeable. They show no significant response to other neurotransmitters. They are potently blocked by the nicotinic antagonist d-tubocurarine but not strongly activated by the agonist nicotine. Arecoline is an effective agonist but with low affinity. The other two subunits ACC-3 (F55D10.5) and ACC-4 (T27E9.9) do not form ligand-responsive homomers but appear to form heteromeric channels with ACC-1 or ACC-2. In phylogenetic analyses, the ACC subunits, along with four other predicted subunit genes (K10D6.1, C50B6.11, F47A4.1 and Y71D11A.5), form a clade. We predict that these eight genes encode a family of acetylcholine-gated chloride channel subunits, which is most closely related to the serotonin-gated chloride channel subunit MOD-1. We are currently trying to determine the function of these channels. ACC-1 and 2 promoter::GFP fusions are expressed in apparently non-overlapping subsets of ring neurons and ACC-1 is expressed in the pair of M3 neurons in the pharynx whereas ACC-2 is expressed in enteric muscles. We have generated transgenic worms expressing RNAi hairpin constructs for ACC-1 and 2 driven by the endogenous promoters and are analyzing the effects of reduced ACC-1 and 2 expression in behavioral assays. (Kehoe, J., 1972, J. Physiol. 225, 85-114; Putrenko et al., 2005, J. Biol. Chem. 280, 6392-6398) JF - International Worm Meeting TI - Is acetylcholine a fast inhibitor? A family of genes encodes acetylcholine-gated chloride channels in C. elegans. KW - acc-1 KW - acc-2 KW - acc-3 KW - acc-4 KW - c50b611 KW - c53d63 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - elegans KW - f47a41 KW - f55d105 KW - f58g64 KW - k10d61 KW - lgc-46 KW - lgc-47 KW - lgc-48 KW - lgc-49 KW - meeting_abstract KW - nematode KW - t27e99 KW - wormbase KW - y71d11a5 AU - Putrenko, Igor AU - Zakikhani, Mahvash AU - Dent, Joseph PY - 2005/// UR - http://www.wormbase.org/db/misc/paper?name=WBPaper00026296 ER -