Hyperpolarization activated cation current in epilepsy
Category: Current
Published Date
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Epilepsy is the most common chronic neurological disorder imposing a significant social and economic impact on our society. There is an obvious clinical need for improved therapeutics that will only be realised by a better understanding of this disease. A key goal in our understanding of this disease is to define the molecular participants involved in the epileptogenic process and attribute functional consequences to them. One candidate class of molecules is the hyperpolarisation activated cation channels (HCNs). There are a number of studies that have showed changes in HCN expression and function during the development of epilepsy, but their impact on seizure susceptibility remains unclear. This motivates our hypothesis: that selective up and down regulation of HCN expression can modulate seizure susceptibility. The aim of this project is to take advantage of state-of-the-art recombinant viral gene delivery methods to change HCN1 and HCN2 levels. Injection of these tools into different parts of the brain will allow us to determine if changing HCN protein expression can produce or 'rescue' epilepsy. Also, together with our collaborators we are the first to find a mutation in the HCN gene that may act to increase the susceptibility of an individual's likelihood of getting epilepsy. The research aim is to determine the impact of this mutation on channel function and how this may change seizure thresholds.
