M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation.

ABSTRACT: Potassium chloride co-transporter 2 (KCC2), a major chloride transporter that maintains GABA_A receptor inhibition in mature mammalian neurons, is down-regulated in the hippocampus during epileptogenesis. Impaired KCC2 function accelerates or facilitates seizure onset. Calpain, with two main subtypes of m- and μ-calpain, is a Ca²⁺-dependent cysteine protease that mediates the nonlysosomal degradation of KCC2. Although recent studies have demonstrated that calpain inhibitors exert antiepileptic and neuroprotective effects in animal models of acute and chronic epilepsy, whether calpain activation affects seizure induction through KCC2 degradation remains unknown. Our results showed that: (1) Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented convu

SUBMITTER: Wan L 

PROVIDER: S-EPMC6110871 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature