Neuromodulation of voltage-gated sodium channels by Gβ1γ2 subunits: Implications for GNB1-linked encephalopathy.

ABSTRACT: Guanine nucleotide-binding protein Gβγ subunits are ubiquitous signaling molecules that interact with numerous effector proteins in neurons, including voltage-gated sodium, calcium, and potassium channels. We show that Gβγ subunits associate with voltage-gated sodium channels (Na_vs) in mouse brain, and co-expression of a prominent Gβγ complex, Gβ1γ2, leads to functional inhibition of brain Na_v α subunit subtypes Na_v1.1 and Na_v1.6 in heterologous cells. Gβ1γ2 co-expression shows subtype-selective effects on Na_v1.1 and Na_v1.6 in the presence of Na_vβ1 subunit co-expression, and in response to prepulse voltage changes. De novo variants in GNB1, encoding the Gβ1 subunit, are linked to GNB1 encephalopathy (GNB1-E). Usin

SUBMITTER: Denomme N 

PROVIDER: S-EPMC12531703 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature