Prolonged seizure activity causes caspase dependent cleavage and dysfunction of G-protein activated inwardly rectifying potassium channels.

ABSTRACT: Recurrent high-frequency epileptic seizures cause progressive hippocampal sclerosis, which is associated with caspase-3 activation and NMDA receptor-dependent excitotoxicity. However, the identity of caspase-3 substrates that contribute to seizure-induced hippocampal atrophy remains largely unknown. Here, we show that prolonged high-frequency epileptiform discharges in cultured hippocampal neurons leads to caspase-dependent cleavage of GIRK1 and GIRK2, the major subunits of neuronal G protein-activated inwardly rectifying potassium (GIRK) channels that mediate membrane hyperpolarization and synaptic inhibition in the brain. We have identified caspase-3 cleavage sites in GIRK1 (³⁸⁷ECLD³⁹⁰) and GIRK2 (³⁴⁹YEVD³⁵²). The YEVD motif is highly conserved

SUBMITTER: Baculis BC 

PROVIDER: S-EPMC5615076 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature