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  • Title: Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin.
    Author: Elleman AV, Devienne G, Makinson CD, Haynes AL, Huguenard JR, Du Bois J.
    Journal: Nat Commun; 2021 Jul 07; 12(1):4171. PubMed ID: 34234116.
    Abstract:
    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.
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