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Acetylcholine Receptor Alpha 3 Beta 4 - " Nicotinic a3b4 receptors recorded on Nanion's Patchliner"

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The nicotinic acetylcholine receptor (nAChR) is a member of the ligand-gated ion channel superfamily which includes GABAA, 5HT3, NMDA and glycine receptors. It is a cation-permeable ion channel activated by the neurotransmitter acetylcholine and the natural alkaloid, nicotine. Neuronal nAChR are pentameric and functional channels are formed from a repertoire of nine α (α2 to α10) and three β subunits (β2 to β4). Most nAChR exist as heteromers with the stoichiometry 2α to 3β, however some α subunits function as homomers, these being α7 or α9. nAChR have been proposed to play a role in many neurological disorders such as Alzheimer’s Disease, Parkinson’s, Tourette’s Syndrome and depression. mRNA for the α3 and β4 subunits is found in the mammalian CNS and PNS, in particular automomic ganglion cells and chromaffin cells. nAChR containing the α3 subunit are essential for mediating fast synaptic  transmission in the autonomic nervous system and is essential for survival. Block of nicotinic α3β4 receptors by methadone has also been suggested to play a potential role in analgesia. Here we present data collected on a 4- or 8-channel Patchliner showing the potential use of the Patchliner to record nAChR α3β4 currents activated by nicotine. Nicotine activated α3β4 receptors in a concentration dependent manner with an EC50 similar to those reported in the literature. Nicotinic α3β4 receptors could be repetitively activated by nicotine and blocked by mecamylamine, a ganglionic blocker with clinically relevant hypotensive actions, with an IC50 in good agreement with the literature.

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