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| Item Type: | Article |
|---|---|
| Title: | Silencing neurotransmission with membrane-tethered toxins |
| Creators Name: | Auer, S., Stuerzebecher, A.S., Juettner, R., Santos-Torres, J., Hanack, C., Frahm, S., Liehl, B. and Ibanez-Tallon, I. |
| 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. |
| Keywords: | Calcium Channel Blockers, N-Type Calcium Channels, Cultured Cells, Dopamine, Integrases, Pain, Synaptic Transmission, omega-Conotoxins, Animals, Mice, Rats |
| Source: | Nature Methods |
| ISSN: | 1548-7091 |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Number: | 3 |
| Page Range: | 229-236 |
| Date: | March 2010 |
| Official Publication: | https://doi.org/10.1038/nmeth.1425 |
| PubMed: | View item in PubMed |
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