Grant round winners 2009

Certain sub-types of potassium channels have been found to regulate the release of glutamate from pre-synaptic membranes, and dysfunction of these has been proposed to increase brain excitability. Professor Matthew Walker and his colleagues at the Institute of Neurology, University College London, have been awarded £99,396 over 24 months, for a project entitled Potassium channels in epilepsy; in which they will investigate whether prolonged seizures cause changes in the number of these potassium channels, and the effect that this might have on neuronal activity.

The team aims to answer three questions:

  1. Does epilepsy change the number of potassium channels on the pre-synaptic membrane?
  2. If so, does this change alter the amount of glutamate that is released at the pre-synaptic membrane?
  3. If the number of potassium channels is restored to normal, can this reduce seizure activity?

A conventional model of temporal lobe epilepsy will be used, along with standard electrical measurement and staining techniques, to monitor potassium channel activity.

In order to answer the third question, Professor Walker hopes to restore potassium channel activity, using a type of gene therapy involving a certain virus. Experimentally, viruses can be made to carry a particular gene (in this case the potassium channel gene). These modified viruses can be then be injected into living cells. Once inside the cell, some viruses will enter the nucleus (where the cell’s genes are found), taking the additional gene with it. As a result of this, an increased number of potassium channels will be formed.

The findings of this study will increase our understanding of the effect of epilepsy on the brain. Moreover, if the restoration of potassium channel activity is found to have an anti-epileptic effect, this could open an exciting new avenue for epilepsy treatment.