Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin
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作者:
Anna V. Elleman
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机构:Stanford University,Department of Chemistry
Anna V. Elleman
Gabrielle Devienne
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机构:Stanford University,Department of Chemistry
Gabrielle Devienne
Christopher D. Makinson
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机构:Stanford University,Department of Chemistry
Christopher D. Makinson
Allison L. Haynes
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机构:Stanford University,Department of Chemistry
Allison L. Haynes
John R. Huguenard
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机构:Stanford University,Department of Chemistry
John R. Huguenard
J. Du Bois
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机构:Stanford University,Department of Chemistry
J. Du Bois
机构:
[1] Stanford University,Department of Chemistry
[2] Stanford University School of Medicine,Department of Neurology & Neurological Sciences
[3] Columbia University Irving Medical Center,Institute for Genomic Medicine
[4] Columbia University Irving Medical Center,Department of Neurology
来源:
Nature Communications
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12卷
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摘要:
Here we report the pharmacologic blockade of voltage-gated sodium ion channels (NaVs) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaVs to interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of NaVs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to NaV-dependent alterations in action potential propagation, with unmyelinated axons preferentially showing reduced action potential fidelity under conditions of partial NaV block. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and action potential generation.
机构:
Chinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China
Univ Chinese Acad Sci, Beijing, Peoples R ChinaChinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China
Jiang, Daohua
Zhang, Jiangtao
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机构:
Chinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China
Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, MOE, Wuhan, Peoples R ChinaChinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China
Zhang, Jiangtao
Xia, Zhanyi
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机构:
Chinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China
Univ Chinese Acad Sci, Beijing, Peoples R ChinaChinese Acad Sci, Inst Phys, Lab Soft Matter Phys, Beijing, Peoples R China