Year: 2025
Type: article
Abstract: Neuronal voltage-gated sodium channels (Na v ) are major targets for the neurophysiological actions of general anesthetics. In the adult brain, cell type-specific effects on synaptic transmission are attributed to the differential sensitivity to volatile anesthetics of specific Na v subtypes preferentially expressed in mature neurons (Na v 1.1, Na v 1.2, Na v 1.6). Compared to mature neurons, neurons in the developing CNS are more excitable. Since the subtype-selective effects of volatile anesthetics on Na v during early development are unknown, we determined volatile anesthetic effects on Na + currents mediated by Na v 1.3, the principal Na v subtype expressed in developing neurons. Sevoflurane at clinically relevant concentrations inhibited peak Na + current ( I Na ) of human Na v 1.3 heterologously expressed in HEK293T cells in a voltage- dependent manner, induced a −6.1 mV hyperpolarizing shift in the voltage dependence of steady- state inactivation, and slowed recovery from fast inactivation. Na v 1.3-mediated Na + currents also exhibited distinct activation properties associated with neuronal hyperexcitability, including prominent persistent currents and ramp currents, both of which were significantly reduced by sevoflurane. The major neuronal subtype Na v 1.2 showed a more hyperpolarized voltage dependence of steady-state inactivation than Na v 1.3. Consistent with its lower propensity for sustained repetitive firing, Na v 1.2 exhibited minimal persistent and ramp currents, and these were unaffected by sevoflurane. These findings identify subtype-specific effects of the volatile anesthetic sevoflurane on neuronal Na v subtypes and suggest a mechanistic basis for increased anesthetic sensitivity in early neuronal differentiation and maturation.
Source: Scientific Reports
Authors: Jiaxin Xiang, Karl F. Herold, Jimcy Platholi, Hugh C. Hemmings
Institution: Weill Cornell Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4413304081