# Proposed roles of KCNQ2 Channels in Respiratory Homeostasis

> **NIH NIH F31** · UNIVERSITY OF CONNECTICUT STORRS · 2023 · $43,492

## Abstract

PROJECT SUMMARY/ABSTRACT
KCNQ channels are key determinants of neuronal activity, and recent clinical evidence identifies mutations in
KCNQ2 as a cause of neonatal epileptic encephalopathy. Most variants associated with neonatal epileptic
encephalopathy are Loss-of-Function.However, recent work also identified a recurrent KCNQ2 Gain-of-Function
mutation (R201C) in patients with neonatal onset encephalopathy. Patients with both KCNQ2 Loss- and Gain-
of-Function mutations exhibit respiratory dysfunction including central hypoventilation syndrome, a condition
thought to result from loss of respiratory chemoreception, i.e., the mechanism by which the brain regulates
breathing in response to CO2/H+. The retrotrapezoid nucleus (RTN) is an important chemoreceptor region, and
we have shown previously that KCNQ channels regulate basal activity and neurotransmitter modulation of RTN
chemoreceptors. Therefore, I hypothesize that KCNQ2 channels are the principal KCNQ subunits that control
activity of RTN chemoreceptors. Ipropose that KNCQ2 Gain-of-Functionwill hyperpolarize RTNchemoreceptors
and eliminate their contribution to the drive to breathe, whereas KCNQ2 Loss-of-Function mutations will
destabilize RTN chemoreceptor activity and disrupt modulation by neurotransmitters, thus also contributing to
unstable breathing. Additionally, I will also test whether KCNQ2 dysfunction affects not only the RTN but the
respiratory control circuit in general including other chemoreceptors, inspiratory rhythmogenic pre-Bötzinger
complex neurons, and output respiratory motor neurons. Objectives of this study are to investigate, from the
cellular to system level, contributions of KCNQ2 channels to chemoreceptorfunction and respiratory control. The
two Specific Aims of this project are: 1) determine cellular effects of KCNQ2 on respiratory chemoreception,
inspiratory rhythmgeneration and motor output and 2) determine the essential role of KCNQ2 channels in control
of breathing. The rationale for the proposed research is that by understandingwhether and howKCNQ2 channels
regulate neuronal activity across multiple levels of the respiratory circuit, and respiratory behavior, I will lay a
foundation for development of treatments for respiratory problems like apnea and central hypoventilation
syndrome.

## Key facts

- **NIH application ID:** 10544558
- **Project number:** 5F31HL156470-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Jaseph Soto
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $43,492
- **Award type:** 5
- **Project period:** 2021-01-07 → 2025-01-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10544558

## Citation

> US National Institutes of Health, RePORTER application 10544558, Proposed roles of KCNQ2 Channels in Respiratory Homeostasis (5F31HL156470-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10544558. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*