Gene and protein expression of NKCC1, KCC2 and KCC2 phosphorylated serine (KCC2 ser) 940 were measured 1 h post seizure termination and on PND 15 using RT- PCR and western blot.
Our previous work demonstrates that prenatal stress with betamethasone-induced alterations to the expression of the K<sup>+</sup>/Cl<sup>-</sup> co-transporter (KCC2) in gamma-aminobutyric acid (GABA) interneurons lowers the seizure threshold in exposed animals.
Our results showed that: (1) Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented convulsant stimulation induced KCC2 downregulation, and reduced the incidence and the severity of pentylenetetrazole (PTZ) induced seizures.
Repeated induction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla.
Impairment of Cl<sup>-</sup> extrusion after KCC2 dysfunction has been involved in many central nervous system disorders, such as seizures, neuropathic pain, or spasticity, after a spinal cord injury (SCI).
Mice that lack both KCC2 isoforms die at birth due to severe motor defects, including disrupted respiratory rhythm, whereas mice with a targeted disruption of the first exon of KCC2b survive for up to 2 weeks but eventually die due to spontaneous seizures.