# Identification and validation of the epilepsy associated KCNQ2 complexes in the brain

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $442,750

## Abstract

Abstract/Project Summary
Recent human genetic studies have shown that loss or gain of function variants of the voltage-gated
potassium channel KCNQ2 causes neonatal epileptic encephalopathy. It is currently assumed that
KCNQ2 channels primarily associate with KCNQ3 channels in the brain; however, several studies
have suggested that KCNQ2 channels may also interact with additional transmembrane proteins.
Identifying the KCNQ2 membrane complex in the brain is necessary in order to understand how
KCNQ2 channels dysfunction could lead to epilepsy and to also design better therapeutics. To
address this question, we have developed a new epitope tagged mouse line allowing us to analyze
KCNQ2 affinity purified complexes from the hippocampus and neocortex using mass spectrometry.
Indeed, our preliminary data show that KCNQ2 channels could associate with KCNQ3 as well as
KCNQ5 channels. This finding goes against the current dogma that KCNQ2 only associates with
KCNQ3 channels in the nervous system. Therefore, in this proposal we plan to examine whether
native KCNQ2 complex channels in the brain are comprised of KCNQ3 and KCNQ5 channels. To this
end, we will: (i) establish the presence of KCNQ2/5 or KCNQ2/3/5 complexes in the brain and (ii)
probe the biophysical properties of KCNQ2/5-containing KCNQ channels. The proposed research will
make a significant contribution to our broader understanding of how KCNQ2, KCNQ3, and KCNQ5
channels control neuronal excitability, and build a foundation for preventing and treating disorders
associated with neuronal KCNQ dysfunction.

## Key facts

- **NIH application ID:** 10042815
- **Project number:** 1R21NS118262-01
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Heun Soh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,750
- **Award type:** 1
- **Project period:** 2020-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042815

## Citation

> US National Institutes of Health, RePORTER application 10042815, Identification and validation of the epilepsy associated KCNQ2 complexes in the brain (1R21NS118262-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10042815. Licensed CC0.

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