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Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin.

ABSTRACT: Here we report the pharmacologic blockade of voltage-gated sodium ion channels (Na_Vs) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of Na_Vs to interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of Na_Vs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to Na_V-dependent alterations in action potential propagation, with unmyelinated axons preferentially showing reduced action potential fidelity under conditions of partial Na_V block. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and action potential generation.

SUBMITTER: Elleman AV

PROVIDER: S-EPMC8263607 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin.

Elleman Anna V AV Devienne Gabrielle G Makinson Christopher D CD Haynes Allison L AL Huguenard John R JR Du Bois J J

Nature communications 20210707 1

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 di ...[more]

PMID: 34234116

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