Ethosuximide: Subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels.

Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.

Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.