# Perturbed Sodium and Calcium Fluxes in Atrial Fibrillation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $393,854

## Abstract

PROJECT SUMMARY: Atrial fibrillation (AF) is the most common cardiac arrhythmia (affecting ~1-2% of the
general population), resulting in markedly reduced quality of life, and increased mortality, due to a combination
of altered hemodynamics, progressive atrial and ventricular dysfunction, and embolic stroke. Patients with
sporadic AF episodes (paroxysmal AF) are more amenable to rhythm control treatment, but limitation in current
pharmacotherapy causes paroxysmal AF to progress to persistent and chronic AF, characterized by extensive
remodeling that facilitates AF maintenance (“AF begets AF”). The development of urgently needed new
strategies for AF treatment hinge upon improved understanding of how abnormalities in cellular function
(remodeled ion channels, Ca and Na handling, and cellular signaling), together with neurohormonal regulation
trigger and sustain arrhythmia in the atria. Understanding the interactions of these complex biochemical and
biophysical functions requires quantitative systems models that also integrate over multiple physical scales. To
address this complex problem, we aim at developing an integrative and quantitative modeling and simulation
framework, incorporating data from experimental sources, to investigate emerging questions in AF. We
propose a closely integrated combination of experimental and computational studies that takes advantage of
interdisciplinary synergy between Drs. Grandi & Chiamvimonvat at UC Davis and Dr. Dobrev at
Universitätsklinikum Essen. The project will develop and validate a suite of modeling tools used to investigate
mechanistically: (1) how derangements in Ca and Na homeostasis, CaMKII hyperactivation, and β-adrenergic
challenge contribute to cellular afterdepolarizations and triggered activity in early and chronic human AF; (3)
the efficacy and safety (AF-selectivity) of antiarrhythmic drugs targeting cardiac Na channels and atrial-specific
small conductance Ca-activated K channels, to facilitate rational drug design. We contend that understanding
how CaMKII signaling synergizes with ionic and Ca and Na handling remodeling, as well as neurohormonal
regulation, may shed mechanistic insight into AF management. Each aim includes formulation and sensitivity
analysis of new models (Dr. Sobie is a consultant), validation studies with human samples, and testing of
specific hypotheses. Models and data will be distributed freely and widely via software and database
infrastructure supported by Dr. Grandi's lab and scientific networking sites.

## Key facts

- **NIH application ID:** 9927494
- **Project number:** 5R01HL131517-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Eleonora Grandi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,854
- **Award type:** 5
- **Project period:** 2016-06-01 → 2021-08-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927494

## Citation

> US National Institutes of Health, RePORTER application 9927494, Perturbed Sodium and Calcium Fluxes in Atrial Fibrillation (5R01HL131517-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9927494. Licensed CC0.

---

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