The volatile anesthetic isoflurane differentially inhibits voltage-gated sodium channel currents between pyramidal and parvalbumin neurons in the prefrontal cortex.

Background: How volatile anesthetics work remains poorly understood. Modulations of synaptic neurotransmission are the direct cellular mechanisms of volatile anesthetics in the central nervous system. Volatile anesthetics such as isoflurane may reduce neuronal interaction by differentially inhibiting neurotransmission between GABAergic and glutamatergic synapses. Presynaptic voltage-dependent sodium channels (Na _v ), which are strictly coupled with synaptic vesicle exocytosis, are inhibited by volatile anesthetics and may contribute to the selectivity of isoflurane between GABAergic and glutamatergic synapses. However, it is still unknown how isoflurane at clinical concentrations differentially modulates Na _v currents between excitatory and inhibitory neurons at the tissue level.
Methods: In this study, an electrophysiological recording was applied in cortex slices to investigate the effects of isoflurane on Na _v between parvalbumin (PV ⁺ ) and pyramidal neurons in PV-cre-tdTomato and/or vglut2-cre-tdTomato mice.
Results: Isoflurane at clinically relevant concentrations produced a hyperpolarizing shift in the voltage-dependent inactivation and slowed the recovery time from the fast inactivation in both cellular subtypes. Since the voltage of half-maximal inactivation was significantly depolarized in PV ⁺ neurons compared to that of pyramidal neurons, isoflurane inhibited the peak Na _v currents in pyramidal neurons more potently than those of PV ⁺ neurons (35.95 ± 13.32% vs. 19.24 ± 16.04%, P = 0.036 by the Mann-Whitney test).
Conclusions: Isoflurane differentially inhibits Na _v currents between pyramidal and PV ⁺ neurons in the prefrontal cortex, which may contribute to the preferential suppression of glutamate release over GABA release, resulting in the net depression of excitatory-inhibitory circuits in the prefrontal cortex.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Qiu, Yang, Liu, Zhao, Li, Zhu, Liang and Zhou.)