# Distinct Ion Channel Pools and Intercalated Disk Nanoscale Structure Regulate Cardiac Conduction

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $737,202

## Abstract

PROJECT SUMMARY
Critical electrogenic proteins responsible for maintaining cardiac excitability and conduction, including
sodium channels (NaV1.5), inward-rectifying potassium channels (Kir2.1), L-type calcium channels
(Cav1.2), sodium-potassium ATPase (NKA), and sodium-calcium exchanger (NCX) have been
identified to reside in distinct ion channel ‘pools,’ with localization at the cell-cell junction, the
intercalated disk (ID). These distinct ion channel pools suggest regulation via both ‘global’ and ‘local’
control mechanisms. Within the ID, heterogeneous nanoscale structure results in channels
concentrating around gap junctions and mechanical junctions, forming specialized nanodomains.
ID nanodomains perturbation can induce proarrhythmic conduction defects, and disruption of these
nanodomains has been identified in human arrhythmia patients, suggesting that these sites are key
determinants of conduction. However, ID nanoscale structure and molecular organization and their
implications for functional electrophysiology have yet to be systematically investigated in health or
disease.
In this project, we will undertake the first-ever comprehensive and granular quantification of ID structure
and molecular organization using cutting-edge light and electron microscopy techniques and
computational analysis. Further, we will develop a novel computational modeling framework to
incorporate experimental measurements of these distinct ion channel pools (lateral membrane and ID)
and ID nanoscale structure to assess regulation of tissue-scale cardiac conduction, for direct
comparison with optical mapping of murine myocardium. Simulations will extend predictions to
conduction in human ventricles and predict how both chronic and acute ID perturbations impact
conduction in conjunction with additional functional defects, including non-ischemic heart failure.
Upon successful completion of these aims, we will produce a new theoretical underpinning for which
distinct ion channel pools and intercalated disk nanoscale structure confer a ‘global/local control’ of
cardiac conduction and suggest new therapeutic approaches to preserve conduction during disease
progression.

## Key facts

- **NIH application ID:** 10831067
- **Project number:** 5R01HL165751-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Thomas Jeffrey Hund
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $737,202
- **Award type:** 5
- **Project period:** 2023-04-20 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831067

## Citation

> US National Institutes of Health, RePORTER application 10831067, Distinct Ion Channel Pools and Intercalated Disk Nanoscale Structure Regulate Cardiac Conduction (5R01HL165751-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10831067. Licensed CC0.

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