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.

Voltage-gated sodium channel (NaV) activity underlies electrical signaling, synaptic release, circuit function, and, ultimately, behavior. Molecular tools that enable precise control of NaV subpopulations make possible temporal regulation of neuronal activity and cellular communication. To rapidly modulate NaV currents, we have rendered a potent NaV inhibitor, saxitoxin, transiently inert through chemical protection with a novel nitrobenzyl-derived photocleavable group. Light-induced uncaging of the photocaged toxin, STX-bpc, effects rapid inhibitor release and focal NaV block. We demonstrate the efficacy of this reagent for manipulating action potentials in mammalian neurons and brain slice and for altering locomotor behavior in larval zebrafish. Photo-uncaging of STX-bpc is a non-invasive, effective method for reversible, spatiotemporally precise tuning of NaV currents, application of which requires no genetic manipulation of the biological sample.

SummaryHere 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.

In this article the grant number R01 GM117263 relating to NIH for J. Du Bois was inadvertently omitted. The original article has been corrected.

Background: The hepatitis B vaccine (HBV) is recommended at birth to prevent perinatal hepatitis B transmission; however, many newborns still do not receive HBV. The extent to which planned out-of-hospital births, which have increased over the past decade, are associated with nonreceipt of the HBV birth dose is unknown. The purpose of this study was to determine whether a planned out-of-hospital birth location is associated with the nonreceipt of the HBV birth dose. Methods: We performed a retrospective cohort study of all births from 2007 to 2019 recorded in the Colorado birth registry. χ 2 analyses were used to compare maternal demographics by birth location. Univariate and multiple logistic regression were used to evaluate the association of birth location with nonreceipt of the HBV birth dose. Results: In total 1.5% of neonates born in freestanding birth centers and 0.1% of neonates born at a planned home birth received HBV compared to 76.3% of neonates born in a hospital location. After adjusting for confounders, this translated to a large increase in the odds of not receiving HBV compared to in-hospital births [freestanding birth center (aodds ratio (aOR): 172.98, 95% confidence interval (CI): 136.98–219.88); planned home birth (aOR: 502.05, 95% CI: 363.04–694.29)]. Additionally, older maternal age, White/non-Hispanic race and ethnicity, higher income, and private or no insurance were associated with nonreceipt of the HBV birth dose. Conclusions: Planned out-of-hospital birth is a risk factor for nonreceipt of the HBV birth dose. As births in these locations become more common, targeted policies and education are warranted.