# CaMKII activation and regulation in adult cardiac myocytes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $627,722

## Abstract

Project Summary/ Abstract
Ca-Calmodulin dependent protein kinase (CaMKII) is an important regulator of cardiac function,
and dysfunction in pathological states, regulating ion channels, Ca transporters, myofilaments
and nuclear transcription. CaMKII may normally fine-tune these processes. But in pathological
conditions chronic autonomous CaMKII over-activation can hyerphosphorylate targets,
contributing to arrhythmogenesis due to acute effects on several ion channels and Ca-handling
proteins. Chronic CaMKII activation is also a hallmark of several pathological states and acute
or genetic CaMKII inhibition can reduce arrhythmias and the progression of HF. Thus
understanding fundamental aspects of CaMKII regulation in cardiac myocytes is critical
understanding dysfunction and potential therapeutics. We and others discovered several novel
post-translational modifications (PTMs) that can trap CaMKII in an activated state, rather than
turning on & off rapidly with local Ca transients. Autophosphorylation, oxidation, GlcNAcylation
and S-nitrosylation within a regulatory hotspot on CaMKII creates memory and autonomous
activity, even when Ca/CaM falls. The functional synergy among these PTMs is unknown, but
will be directly measured in myocytes in Aim 1. Dogma has been that CaMKII-dodecamers
neither exchange subunits nor move appreciably in myocytes, but our preliminary data upends
both dogmas, and this will be elucidated in Aim 2. S-nitrosylation, the newest regulatory PTM,
can either promote autonomous activation (C290) or inhibit Ca/CaM activation (C273). Aim 3
will test the functional impact of these sites in adult myocytes and in acute ischemia/reperfusion
and long-term pressure overload in intact animals. We will use multiple innovative fluorescence
tools and methods, and animals to test these 3 major CaMKII Aims. The proposed studies will
have major impact on our understanding of how CaMKII activity is regulated in heart, in ways
that promote pathology and might be targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 9905549
- **Project number:** 5R01HL142282-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Donald M Bers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,722
- **Award type:** 5
- **Project period:** 2018-04-18 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905549

## Citation

> US National Institutes of Health, RePORTER application 9905549, CaMKII activation and regulation in adult cardiac myocytes (5R01HL142282-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9905549. Licensed CC0.

---

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