KCC2

The many faces of KCC2 in the generation and suppression of seizures

KCC2, best known as the neuron-specific chloride extruder that sets the strength and polarity of GABAergic Cl-currents, is a multifunctional molecule which interacts with other ion-regulatory proteins and (structurally) with the neuronal cytoskeleton. Its multiple roles in the generation and suppression of seizures have been widely studied. In my talk, I will address some fundamental issues which are relevant in this field of research: What are EGABA shifts about? What is the role of KCC2 in shunting inhibition? What is meant by “the balance between excitation and inhibition” and, in this context, by the “NKCC1/KCC2 ratio”? Is down-regulation of KCC2 following neuronal trauma a manifestation of adaptive or maladaptive ionic plasticity? Under what conditions is K-Cl cotransport by KCC2 promoting seizures? Should we pay more attention to KCC2 as molecule involved in dendritic spine formation in brain areas such as the hippocampus? Most of these points are of potential importance also in the design of KCC2-targeting drugs and genetic manipulations aimed at combating seizures.

Two candidate K-Cl cotransporter 2 (KCC2) enhancers prevent epileptiform activity in vitro and in vivo

Enhancing potassium-chloride co-transporter-2 (KCC2) function in neurons by targeting protein-protein interactions

KCC2 function is altered in the indirect pathway of the basal ganglia in Huntington’s Disease

KCC2-mediated regulation of chronic benzodiazepine action

Pro- and mature-brain-derived neurotrophic factor (BDNF) control neuronal chloride homeostasis through cation-chloride co-transporter activity KCC2

Non-canonical role of NKCC1 in neurons by regulating KCC2 function

Selective NKCC1 Inhibitors for the Treatment of Autism, Down syndrome and Brain Disorders with defective NKCC1/KCC2 ratio

Effects of VEGF and BDNF administration on KCC2 levels in axotomized extraocular motoneurons

FENS Forum 2024

Functional upregulation of KCC2 in cortical interneurons precedes that in glutamatergic principal neurons

FENS Forum 2024

K-Cl cotransporter KCC2 function is impaired in D2 receptor-expressing medium spiny neurons in a mouse model of Huntington's disease

FENS Forum 2024

KCC2 pharmacological targeting as a novel therapeutic strategy to rescue cognitive decline of aging

FENS Forum 2024

KCC2a controls KCC2b membrane expression, recycling, and function in mature hippocampal neurons

FENS Forum 2024