# KCNQ2/3 channels and interneuron physiology

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2021 · $346,305

## Abstract

KCNQ2/3 channels have emerged as essential regulators of neonatal brain excitability, highlighted by the
several loss- and gain-of-function KCNQ2 and KCNQ3 variants that have been identified in patients with
neonatal and infantile epileptic encephalopathy. Therefore, an improved understanding of the function of
neuronal KCNQ2/3 channels in the brain is paramount for developing new therapeutics for neonatal epilepsy.
Over the last several years, we have made progress in determining the differential roles of KCNQ2 and
KCNQ3 channels in controlling pyramidal neuron excitability and in mediating multiple membrane
conductances. Here we propose experiments to tackle important outstanding questions regarding the function
and properties of KCNQ2/3 potassium channels in interneurons. Interneurons are critical for shaping the
activity of neuronal populations and promoting the development of excitatory synaptic circuits. KCNQ2/3
channels are expressed early in development when interneurons have not yet fully developed their clade of
unique potassium channels, raising the possibility that KCNQ2/3 channels might control interneuron properties
at early developmental stages. One explanation is that a decrease in interneuron excitability leads to the
hyperexcitability phenotype of the gain-of-function KCNQ2/3 variants in epileptic encephalopathy. Thus,
elucidating the role of KCNQ2/3 channels in interneuron excitability and exploring the effects of known gain-of-function KCNQ2/3 variants will shed new insights into cortical physiology in health and disease. To this end,
we will: (i) determine the function of KCNQ2/3 channels in immature parvalbumin (PV)- and
somatostatin (SST)-positive interneurons using cell-type specific genetics, (ii) determine whether
Kcnq2/3 ablation from interneurons leads to network excitability ex vivo and in vivo, and (iii) determine
whether gain-of-function KCNQ2/3 variants lead to interneuron hypoexcitability and subsequent
excitatory network hyperexcitability. The proposed research will significantly contribute to our broader
understanding of how KCNQ2/3 channels control neuronal excitability, building a foundation for the prevention
and treatment of neurological disorders such as pediatric epilepsy.

## Key facts

- **NIH application ID:** 10175062
- **Project number:** 5R01NS101596-05
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Anastasios Tzingounis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,305
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175062

## Citation

> US National Institutes of Health, RePORTER application 10175062, KCNQ2/3 channels and interneuron physiology (5R01NS101596-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10175062. Licensed CC0.

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