Pathophysiological contributions of T-type calcium channel variation towards thalamocortical network hyperexcitability and absence epilepsy

More than 50 million people worldwide suffer from epilepsy. Approximately 90 percent of those treated with current drugs experience significant side effects, and around 30 percent do not respond to current medical treatments at all. Therefore, significantly better treatments are required to improve the quality of life for epilepsy sufferers in Canada and worldwide. To achieve this, a far greater understanding of how the brain works both normally and during seizures is necessary.

Epilepsy is a difficult disorder to study in humans; however, in the 1980s, a strain of rats that naturally suffer from a type of seizure very similar to the human condition and involving the same brain regions was identified. These rats are extremely useful in helping us understand the causes of epilepsy in humans and test new drugs being developed to treat epilepsy. Two years ago, Dr. Stuart Cain’s research characterized a newly discovered genetic mutation in the epileptic rat strain responsible for a large portion of seizures. Epileptic seizures can be caused by changes in the way certain brain nerve cell proteins, known as "calcium channels," conduct electricity — the mutation characterized by Dr. Cain alters the way in which a specific type of calcium channel conducts electrical signaling. This was significant as these particular calcium channels are able to generate patterns of electrical pulses, known as “firing patterns,” predicted to contribute to epileptic seizures.

Dr. Cain’s research project aims to determine how the calcium channel mutation alters communication between nerve cells and affects different firing patterns. His laboratory is the only site in North America currently studying the epileptic rat strain. Understanding what causes the firing properties of epileptic nerves to change during seizures should allow the design of new drug treatments with the ability to block these changes directly, and to also reduce side effects compared to many of the broad-target drugs currently used clinically.