Many types of epilepsy are the result of inherited defects in ion channels. Researchers from Houston, Texas, USA, have reported a case where two such changes (which each on their own cause a different type of epilepsy) work against each other, cancelling their effects when they occur together.

Ion channels and channelopathies
Ion channels are tiny pores on the surface of nerve cells in the brain which allow electrically-charged particles to flow into or out of the cell. These particles are called ions. An ion channel will only let through a single type of ion (for example, sodium, potassium or chloride) and then only in one direction. Nerve cells send messages electrically by controlling the opening and closing of ion channels, thus moving electrical charges about.

If the gene that is the blueprint for a type of ion channel is altered, the channels may not work properly, or there may not be enough of them, or they may not form in the right cells in the brain. Changes in these genes can therefore fundamentally alter the way brain cells communicate. Types of epilepsy known to be caused in this way are called channelopathies. Each different ion channel gene change can cause quite a different type of epilepsy.

Animal models
Many of these genetic mutations are investigated in breeds of mice. Those which have a mutation in a gene called Kcna1, which codes for a potassium channel, develop seizures starting in the limbic system of the brain (which controls mood and instincts) and also have a tendency to sudden death. Mice which have a mutation in the Cacna1a gene, which controls sodium channel formation, have absence seizures.

Professor Jeffrey Noebels and his team at Baylor College of Medicine reported the characteristics of a breed of mice which had both these mutations. Animals with both mutations have neither type of epilepsy. The changes that each gene causes to the ion channels work against each other. The sodium channel mutation decreases the excitability of the brain and counters the limbic epilepsy caused by the Kcna1 mutation; this mutation in return stops the absence seizures caused by the sodium channel mutation.

This research was published November 2007 in the journal Nature Neuroscience. It is an interesting demonstration of just how complicated the genetics of epilepsy can be. It shows that it will be impossible to run a 'test for epilepsy' on just one gene, as how this gene interacts with all the others can be so significant.

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