# Involvement of TWIK-related K+ channel in cardiac disease and arrhythmia

> **NIH NIH F31** · OHIO STATE UNIVERSITY · 2022 · $34,778

## Abstract

Project Summary
 Heart failure (HF) is a leading cause of death in the United States and is growing in prevalence. HF
patients are at higher risk for sudden cardiac death from ventricular arrhythmias, and despite major strides in
understanding the pathology of HF, current arrhythmia treatments are limited by efficacy, cost, and risk of
procedural complications. Although the field has identified a host of electrophysiological and structural changes
in HF, the precise link between chronic stress and arrhythmia remains to be defined.
 Recent studies have identified a novel role for the two-pore domain background K channel TREK1 in
regulating arrhythmia susceptibility and excitability. Previous work from our lab has found that the actin-
associated cytoskeletal protein βIV-spectrin orchestrates TREK1 membrane localization. However, how
spectrin modulates TREK1 function, and how disruption of a TREK1/spectrin complex contributes to disease,
is still largely unknown. Preliminary data from our lab suggests that in the absence of interaction with spectrin,
TREK1 current-voltage relationships and reversal potentials are shifted. This suggests a change in ion
permeability, which would be consistent with studies in patients and rat models that have shown that TREK1
may become permeable to Na as a result of mutations or alternative translation initiation.
 Based on these preliminary studies, the central hypothesis of my proposal is that loss of βIV-spectrin in
response to chronic stress promotes aberrant TREK1 activity leading to altered myocyte ion homeostasis and
increased arrhythmia susceptibility. I will employ a combination of optical mapping, electrophysiology, and
molecular biology techniques to determine the role of the TREK1/spectrin complex in the regulation of cardiac
excitability. Additionally, I will evaluate cardiac electrophysiology, Ca and Na handling, and protein co-
localization of hearts subjected to pressure overload to assess whether dysregulation of TREK1 during chronic
stress promotes aberrant ion homeostasis and electrical remodeling that is pro-arrhythmic. Finally,
pharmacological and gene-based interventions aimed at preserving normal TREK1 activity will be evaluated for
their ability to preserve cardiac electrical function in vivo during chronic stress. Overall, this study has the
potential to suggest novel therapeutic approaches for preventing proarrhythmic triggers in HF patients,
ultimately advancing the NIH’s mission “to enhance health, lengthen life, and reduce illness and disability.”

## Key facts

- **NIH application ID:** 10387461
- **Project number:** 1F31HL162547-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Cemantha ML Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,778
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387461

## Citation

> US National Institutes of Health, RePORTER application 10387461, Involvement of TWIK-related K+ channel in cardiac disease and arrhythmia (1F31HL162547-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10387461. Licensed CC0.

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