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NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor mediated currents
Blocking dephosphorylation of Ser940 reduced the glutamate-induced downregulation of KCC2 and substantially improved the maintenance of hyperpolarizing GABAergic inhibition.
Modulation of neuronal activity by phosphorylation of the K–Cl cotransporter KCC2
Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy
The report of two non‐synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE) are described and suggest genetically encoded impairment of K CC2 functional regulation may be a risk factor for the development of human IGE.
Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures
- Yvonne E. Moore, T. Deeb, Heramb Chadchankar, N. Brandon, S. Moss
- BiologyProceedings of the National Academy of Sciences
- 17 September 2018
It is determined that potentiating Cl− extrusion in vivo reduces susceptibility to chemoconvulsant-induced seizures and highlights depolarizing GABA as a key contributor to the pathological neuronal synchronization seen in epilepsy.
Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation.
KCC2 activity is critical in limiting the onset and severity of status epilepticus
It is shown that SE leads to rapid dephosphorylation of residue serine 940, and it is demonstrated that deficits in S940 phosphorylation directly contribute to the onset and severity of SE.
Regulation of GABAARs by phosphorylation.
Tonically Active GABAA Receptors in Hippocampal Pyramidal Neurons Exhibit Constitutive GABA-Independent Gating
It is hypothesized that GABAA receptors, constitutively active in the absence of GABA, mediate tonic current in hippocampal pyramidal neurons; the failure of gabazine to block tonicCurrent reflects a lack of negative intrinsic efficacy of the antagonist.
Possible alterations in GABAA receptor signaling that underlie benzodiazepine‐resistant seizures
Evidence supporting the role of altered GABAA receptor function as the major underlying cause of benzodiazepine‐resistant SE in both humans and animal models is discussed.