Language
English
Publication Date
2-1-2026
Journal
Journal of Molecular and Cellular Cardiology
DOI
10.1016/j.yjmcc.2025.11.013
PMID
41297693
PMCID
PMC12968982
PubMedCentral® Posted Date
3-10-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the expression of Ca2+-handling proteins. This review examines the mechanisms governing cAMP levels in the sarcoplasmic reticulum nanodomain and their role in regulating RyR2 function in healthy and diseased hearts.
Keywords
Cyclic AMP, Ryanodine Receptor Calcium Release Channel, Humans, Animals, Myocytes, Cardiac, Sarcoplasmic Reticulum, Calcium, Heart Diseases, Myocardium, Calcium Signaling, Signal Transduction, Atrial fibrillation, Cyclic adenosine monophosphate, Heart failure, Nucleoside-diphosphate kinases, Ryanodine receptor
Published Open-Access
yes
Recommended Citation
Hulsurkar, Mohit M; Ong, Isabelle; Keefe, Joshua A; et al., "Cyclic Amp-Dependent Regulation of Ryanodine Receptors in Healthy and Diseased Hearts" (2026). Faculty, Staff and Students Publications. 6604.
https://digitalcommons.library.tmc.edu/baylor_docs/6604