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Compensatory rearrangement of parvalbumin interneuron voltage-gated sodium channel subunits in a mouse model of Dravet syndrome
Journal article   Open access   Peer reviewed

Compensatory rearrangement of parvalbumin interneuron voltage-gated sodium channel subunits in a mouse model of Dravet syndrome

Ania K Dabrowski, Ala Somarowthu, Sophie R Liebergall, Damaris N Lorenzo and Ethan M Goldberg
Epilepsia (Copenhagen)
06/08/2026
DOI: 10.1002/epi.70336
PMID: 42257687
url
https://doi.org/10.1002/epi.70336View
Published (Version of record) Open Access

Abstract

Heterozygous loss-of-function variants in the gene SCN1A, which encodes the voltage-gated sodium channel (VGSC) pore-forming (α) subunit Na 1.1, lead to a spectrum of neurological disease, including Dravet syndrome. Na 1.1 is prominently expressed at the proximal portion of the axon initial segment (AIS) of fast-spiking γ-aminobutyric acidergic parvalbumin-expressing inhibitory interneurons (PV+INs). In Dravet syndrome (Scn1a haploinsufficient) mice, action potential firing is impaired in PV+INs during postnatal development; however, in mature animals, PV+IN fast-firing frequency has recovered. We used detailed immunohistochemistry and microscopy to probe the mechanism of this functional recovery, investigating potential upregulation of other brain-expressed VGSC subunits at the PV+IN AIS. We found a specific upregulation of Na 1.6 immunofluorescence at the AIS of PV+INs in adult (but not developing) Scn1a mice compared to wild type, with no upregulation of other brain-expressed subunits Na 1.2 or Na 1.3. These results demonstrate one mechanism through which epilepsy-related gene variants reorganize the developing brain and enact endogenous changes that may be at least partially compensatory.
 axon initial segment NaV1.1 voltage‐gated sodium channels NaV1.6 Dravet syndrome SCN1A

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