Differential roles of Na_V1.2 and Na_V1.6 in neocortical pyramidal cell excitability.

ABSTRACT: Mature neocortical pyramidal cells functionally express two sodium channel (Na_V) isoforms: Na_V1.2 and Na_V1.6. These isoforms are differentially localized to pyramidal cell compartments, and as such are thought to contribute to different aspects of neuronal excitability. But determining their precise roles in pyramidal cell excitability has been hampered by a lack of tools that allow for selective, acute block of each isoform individually. Here, we leveraged aryl sulfonamide-based molecule (ASC) inhibitors of Na_V channels that exhibit state-dependent block of both Na_V1.2 and Na_V1.6, along with knock-in mice with changes in Na_V1.2 or Na_V1.6 structure that prevents ASC binding. This allowed for acute, pote

SUBMITTER: Garcia JD 

PROVIDER: S-EPMC12263156 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature