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Silencing neurotransmission with membrane-tethered toxins

Official URL:https://doi.org/10.1038/nmeth.1425
PubMed:View item in PubMed
Creators Name:Auer, S. and Stuerzebecher, A.S. and Juettner, R. and Santos-Torres, J. and Hanack, C. and Frahm, S. and Liehl, B. and Ibanez-Tallon, I.
Journal Title:Nature Methods
Journal Abbreviation:Nat Methods
Volume:7
Number:3
Page Range:229-236
Date:March 2010
Keywords:Calcium Channel Blockers, N-Type Calcium Channels, Cultured Cells, Dopamine, Integrases, Pain, Synaptic Transmission, omega-Conotoxins, Animals, Mice, Rats
Abstract:At synaptic terminals, high voltage-activated Ca(v)2.1 and Ca(v)2.2 calcium channels have an essential and joint role in coupling the presynaptic action potential to neurotransmitter release. Here we show that membrane-tethered toxins allowed cell-autonomous blockade of each channel individually or simultaneously in mouse neurons in vivo. We report optimized constitutive, inducible and Cre recombinase-dependent lentiviral vectors encoding fluorescent recombinant toxins, and we also validated the toxin-based strategy in a transgenic mouse model. Toxins delivered by lentiviral vectors selectively inhibited the dopaminergic nigrostriatal pathway, and transgenic mice with targeted expression in nociceptive peripheral neurons displayed long-lasting suppression of chronic pain. Optimized tethered toxins are tools for cell-specific and temporal manipulation of ion channel-mediated activities in vivo, including blockade of neurotransmitter release.
ISSN:1548-7091
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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