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bioRxiv · 10.1101/2020.11.18.389130

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

Elleman, A. V.·Devienne, G.·Makinson, C. D.·Haynes, A. L.·Huguenard, J. R.·Du Bois, J.
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Abstract

Here we report the pharmacologic blockade of voltage-gated sodium ion channels (NaV) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaV blockade to interrupt action potentials (APs) 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 AP propagation, with unmyelinated axons preferentially showing reduced AP fidelity under conditions of partial NaV blockade. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and AP generation.

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Elleman, A. V., Devienne, G., Makinson, C. D., Haynes, A. L., Huguenard, J. R., Du Bois, J.. 2020-11-20. Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin. https://doi.org/10.1101/2020.11.18.389130

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