Neuronal chloride transport explored for role in epilepsy treatment

Electrophysiologist's from the Institute of Cell biology and Neurobiology at the Charité in Berlin have recently been exploring the complex role of prevailing ionic gradients during GABA_A receptor activation; and the subsequent implications for treatment of epilepsy.

Epilepsy is a severe neurological disorder characteried by unprovoked seizures with a range of distinct symptoms and a complex underlying pathophysiology. There are a number of proposed mechanisms contributing to epileptic syndromes, including disturbances of excitatory and inhibitory neurotransmitter pathways within the brain.

Deisz et al focused on the effect of inhibitory neurotransmitter GABA and it's activation of GABA_A type receptors, they used Scientifica's Patch Pro System, coupled with NPI's SEC-10 amplifier to carry out intracellular recordings from rat and human cortical slices. The GABA_A receptor is primarily a Cl- conducting channel and they therefore applied various pharmacological inhibitors of transmembrane Cl- pathways to the samples to reveal the mechanisms of the aberrant Cl- gradients that are characteristic in human epileptogenic tissue. They also used Molecular Devices data acquisition hardware and software to digitize the data for analysis.

They identified the Potassium coupled Chloride transporter KCC2 as the predominant route maintaining the appropriate Cl- gradient, necessary for normal GABA_A receptor function, and they provide evidence that reduced outward Cl- movement via KCC2 transporters is the first step in disruption of the important chloride regulation in the brain of epileptic individuals.

This study supports further exploration of novel therapeutic drug treatments to alleviate the impact of KCC2 transporter deficits on the worsening of epilepsy.

Rudolf A. Deisz, Thomas-N. Lehmann, Peter Horn, Christoph Dehnicke and Robert Nitsch Components of neuronal chloride transport in rat and human neocortex J Physiol 589.6 (2011) pp 1317-1347