Prediction by Modeling That Epilepsy May Be Caused by Very Small Functional Changes in Ion Channels

Abstract

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..