# Developmental Regulation of Potassium Channels in Hypothalamic Neurons Governing Energy Homeostasis

> **NIH NIH R16** · NORWICH UNIVERSITY · 2022 · $125,294

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of this work is to understand how metabolic signaling can alter the functional development
of energy homeostasis pathways through the modulation of specific ion channels in hypothalamic neurons. The
hypothalamus is a brain region that mediates the regulation of critical metabolic processes throughout the
body. Specialized hypothalamic neurons can integrate the homeostatic balance between food intake and
energy expenditure via peripheral signals, a process that may become dysregulated in obesity and other
metabolic disorders. Evidence indicates that the function of Kv1.3, a voltage-gated potassium channel
governing neuronal excitability and resting membrane potential, can be modulated by circulating peripheral
signals such as insulin, although the role of this modulation in the early development of hypothalamic circuits
remains unclear. The central hypothesis of this proposal is that insulin modulates the developmental
function of Kv1.3 in hypothalamic neurons governing energy homeostasis. The central hypothesis will be
tested with the following specific aims: (1) identify the developmental colocalization of Kv1.3 and the insulin
receptor (IR) in specific hypothalamic nuclei governing energy homeostasis, (2) define how hypothalamic
Kv1.3 channels are functionally modulated by insulin during development, and (3) determine the role of
heteromultimeric Kv1 complexes in channel regulation of the developing hypothalamus. In order to achieve the
experimental objectives, immunofluorescence will be used to identify Kv1.3 and IR protein at different
developmental stages in specific hypothalamic nuclei involved in metabolic function. To test the hypothesis that
insulin regulates neuronal activity via suppression of Kv1.3, brain slices of the avian hypothalamus will be
exposed to exogenous insulin and changes in ion channel function will be recorded using electrophysiological
techniques. Subsequently, in ovo hormone application will be used to determine the long-term effect of insulin
exposure on the electrophysiological function of Kv1.3 in hypothalamic neurons at critical embryological time
points. The physiological effects of Kv1 channel heteromultimerization on the insulin-sensitive function of Kv1.3
channels in hypothalamic neurons will also be explored. This proposal will be the first to elucidate the
developmental role of insulin exposure on Kv1.3 channel function in hypothalamic neurons governing energy
homeostasis. Examining the developmental regulation of Kv1.3 in this embryonic system will provide new
insight fundamental to understanding the early patterning of hypothalamic circuits and may provide further
evidence targeting these potassium channels in the pharmaceutical intervention of metabolic disorders such as
diabetes and obesity.

## Key facts

- **NIH application ID:** 10411760
- **Project number:** 1R16GM145478-01
- **Recipient organization:** NORWICH UNIVERSITY
- **Principal Investigator:** Megan A Doczi
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $125,294
- **Award type:** 1
- **Project period:** 2022-09-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411760

## Citation

> US National Institutes of Health, RePORTER application 10411760, Developmental Regulation of Potassium Channels in Hypothalamic Neurons Governing Energy Homeostasis (1R16GM145478-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10411760. Licensed CC0.

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