# Controlled and Uncontrollable Calcium release in heart

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $390,000

## Abstract

PROJECT SUMMARY:
The long-term goal of this research program is to understand the role of abnormal cardiac
calcium (Ca) handling in the genesis of cardiac arrhythmias. Calcium entry through L-type
calcium channels triggers release of sarcoplasmic reticulum Ca, which then initiates contraction
(excitation contraction coupling – ECC). In the previous funding period we focused on the role
of abnormal calcium release from the sarcoplasmic reticulum, with extension of key findings to
multi-cellular and in vivo settings. In the current proposal we consider the role of a recently
recognized alternate Ca entry pathway, store-operated Ca entry (SOCE), in the myocardium.
SOCE occurs when depletion of SR Ca is sensed by STIM1, prompting Ca entry via
sarcolemmal ORAI1/TRPC channels. Cardiac SOCE has been implicated in the hypertrophic
response and linked to enhanced arrhythmogenesis. Thus, the main goals of this proposal are
to determine 1) how ECC and SOCE coexist in the cardiac myocyte, and 2) how abnormal
interaction(s) between these systems in disease contributes to arrhythmias.
The goals will be addressed through the following specific aims:
Aim 1: Define the cardiac SOCE signaling microdomain and its relationship to the classical ECC
domain;
Aim 2: Define alterations in the SOCE micro-compartment and their arrhythmic mechanisms in
congenital and acquired cardiac arrhythmic disease; and
Aim 3: Assess the antiarrhythmic efficacy of targeting SOCE in the diseased heart.
A combination of genetic and pharmacologic approaches will be used, with key findings in
murine studies extended to human tissues. Our research team has extensive expertise in
studying functional, and structural aspects of cardiac arrhythmogenesis, spanning from
nanodomain signaling mechanisms to in vivo studies, allowing an integrated approach to
execute the specific aims.

## Key facts

- **NIH application ID:** 10489248
- **Project number:** 5R01HL063043-23
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Sandor Gyorke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 1999-09-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489248

## Citation

> US National Institutes of Health, RePORTER application 10489248, Controlled and Uncontrollable Calcium release in heart (5R01HL063043-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10489248. Licensed CC0.

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