Prediction by Modeling That Epilepsy May Be Caused by Very Small Functional Changes in Ion Channels
Evan A Thomas, Christopher A Reid, Samuel F Berhovic, Steven Petrou
ARCHIVES OF NEUROLOGY | AMER MEDICAL ASSOC | Published : 2009
OBJECTIVE: To use computer simulation to perform a "genetic sensitivity" analysis to predict which genes are best positioned to increase risk as well as to predict functionally how variants in these genes might increase network excitability. METHODS: A previously published, biophysically realistic model of the dentate gyrus that included mossy fiber sprouting between granule cells was used to model putative environmental changes associated with temporal lobe epilepsy. Properties of voltage-gated ion channels, either 1 at a time or in combinations, were varied systematically to determine their effect on network excitability. RESULTS: We found that the network is most sensitive to changes in s..View full abstract
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Awarded by NHMRC
This study was supported in part by an Australian National Health and Medical Research Council (NHMRC) Peter Doherty Fellowship (Dr Thomas); a University of Melbourne R. D. Wright Fellowship and NHMRC grant 454655 (Dr Reid); and NHMRC grant 400121.