September 30, 2014

Seizure mutation impairs receptor

Defects in the production of certain receptors are linked to the pathogenesis of genetic epilepsies and fever-induced seizures.

brain and lightning

(iStock)Febrile (fever-induced) seizures are the most common seizure in children under 6 years old and increase risk of developing genetic epilepsies in later life. Some genetic epilepsies present in childhood as febrile seizures.

A mutation in the gamma2 subunit of a GABA-A receptor, which is important for fast inhibitory synaptic transmission, has been linked to febrile seizures. The mutation, R177G, may promote neuronal hyper-excitability due to loss of inhibition.

In the September issue of Neurobiology of Disease, Robert L. Macdonald, M.D., Ph.D. and his colleagues used electrophysiology, flow cytometry, immunoblotting and homology modeling to demonstrate R177G impairs GABA-A receptor production.

Their work suggests that the mutant gamma2 subunits have defects in receptor assembly and/or forward trafficking, resulting in lower expression of the receptor on the cell surface.

These findings support increasing evidence implicating defects in biogenesis of the GABA-A receptor in the pathogenesis of genetic epilepsies as well as febrile seizures, the researchers concluded.

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