Cation leak underlies neuronal hyperexcitability in an HCN1 developmental & epileptic encephalopathy
Channel: The Royal Society of Victoria
Date: 19/08/2021

The HCN1 gene encodes the HCN1 ion channel, which plays a key role in setting and stabilizing the resting membrane potential of neurons. 

Pathogenic variants in HCN1 are known to cause epilepsy, including severe, early-onset epilepsy syndromes such as developmental and epileptic encephalopathy (DEE). To date, 29 confirmed pathogenic variants in HCN1 have been identified to cause epilepsy, with 14 of these variants, including the recurrent de novo HCN1 M305L variant, associated with DEE. 

Although preliminary functional analysis has been conducted on some HCN1 variants, the mechanisms through which changes in HCN1 channel function lead to neuronal hyperexcitability are yet to be examined in detail. This research involved engineering the Hcn1 M294L heterozygous knock-in (Hcn1M294L) mouse, which carries the mouse homologue of the human HCN1 M305L variant and is the first mouse model of HCN1 epilepsy, in order to explore the disease mechanism underlying HCN1 DEE.

Lauren Bleakley is a final year PhD candidate with the Florey Institute of Neuroscience and Mental Health at the University of Melbourne. This presentation titled "Cation leak underlies neuronal hyperexcitability in an HCN1 developmental & epileptic encephalopathy" comprises her entry to the Biomedical and Health Sciences category of the Young Scientist Research Prizes in 2021, an annual competition conducted by the Royal Society of Victoria during National Science Week in Australia. Lauren is the First Prize winner in this category. 

Produced with the support of the Inspiring Victoria program.