NKCC1

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.

Anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome

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

The NKCC1 inhibitor bumetanide restores cortical feedforward inhibition and lessens sensory hypersensitivity in early postnatal Fragile X mice

FENS Forum 2024

Non-canonical role of NKCC1 chloride transporter in neurons: A scaffold protein for SPAK kinase?

FENS Forum 2024

Possible role of NKCC1 in the proliferation of hippocampal neural stem cells during Alzheimer's disease

FENS Forum 2024

Selective NKCC1 inhibitors for the treatment of brain disorders with defective chloride homeostasis

FENS Forum 2024