Research ArticleEpilepsy

Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice

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Science Translational Medicine  18 Nov 2020:
Vol. 12, Issue 570, eabc1492
DOI: 10.1126/scitranslmed.abc1492

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Out of place channels drive seizures

Focal cortical malformations (FCMs) develop in a group of diseases caused by mutations in the mTOR pathway. Patients often develop pharmacoresistant epilepsy; however, the molecular mechanisms underlying seizure occurrence are not completely understood. Now, Hsieh et al. performed in vitro and in vivo studies in a mouse model of FCM to understand the mechanism of seizure generation. The authors showed that ectopic HCN4 channels expressed in FCM neurons were responsible for seizure generation by depolarizing the resting membrane potential. Expression analysis in cortical tissue from patients with FCM showed increased expression of HCN4, suggesting that HCN4 could be targeted for treating seizures in patients with FCM.

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