Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin
Here we report the pharmacologic blockade of voltage-gated sodium ion channels (Na V s) 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 V s to interrupt action po...
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Veröffentlicht in: | Nature communications 2021-07, Vol.12 (1), p.4171-9, Article 4171 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Here we report the pharmacologic blockade of voltage-gated sodium ion channels (Na
V
s) 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
V
s 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
V
s. 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.
Photocaged molecules have advantages in terms of temporal and spatial control compared to conventional pharmacological compounds. The authors present a synthetic saxitoxin derivative affixed to a photocleavable group for precise modulation of Na channels. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-24392-2 |