Brain function is a delicate balance of neuronal excitation and inhibition. The schematic diagram above illustrates inhbitory neuronal responses mediated via the neurotransmitter GABA, and how these are affected by the neuronal Cl- transporters KCC2 and NKCC1. In neonatal neurons (left, A), KCC2 is absent and NKCC1 mediated Cl- influx results in GABA mediated depolarization and excitation. In most adult neurons (middle, B), KCC2-mediated Cl- efflux dominates Cl- homeostasis resulting in GABA mediated hyperpolarization and inhibition (A&B adapted from Ben-Ari, 2002). (C, right) KCC2 is downregulated after adult brain injury resulting in a conversion of GABA response back towards the immature depolarizing phenotype. This research project proposes that loss of KCC2 is a key event in the pathogenesis of temporal loe epilepsy and the maintenance of spontaneous seizures.
Modifying Brain Excitability by Upregulating the KCC2 Chloride Transporter
Professor Junichi Nabekura
National Institute of Physiological Sciences, Okazaki, Japan
Faculty of Medicine
University of NSW - NHMRC Project Grant Project ID: APP1065882