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Updated: Jul 25, 2025

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Emerging Evidence for cAMP-calcium Cross Talk in Heart Atrial Nanodomains Where IP3-Evoked Calcium Release Stimulates
Rebecca-Ann B Burton1, Derek A Terrar1
1Department of Pharmacology, University of Oxford, Oxford, UK.
Insights
Calcium signaling via inositol trisphosphate receptors (IP3Rs) in atrial cells contributes to arrhythmias. Crosstalk between calcium and cAMP pathways in atrial myocytes offers new therapeutic targets for treating atrial fibrillation.
Area of Science:
- Cardiology
- Molecular Physiology
- Biochemistry
Background:
- Atrial arrhythmias, such as atrial fibrillation, pose significant health risks.
- Understanding calcium handling in atrial myocytes is crucial for addressing these conditions.
- Inositol trisphosphate (IP3) plays a key role in calcium signaling within the heart.
Purpose of the Study:
- To elucidate the mechanisms of calcium signaling in atrial myocytes.
- To investigate the interaction between calcium and cAMP pathways in the atria.
- To identify potential therapeutic targets for atrial arrhythmias.
Main Methods:
- Investigated the role of IP3 receptors (IP3Rs) in atrial calcium transients.
- Examined the function of calcium-dependent adenylyl cyclases (AC8 and AC1) in atrial myocytes.
- Studied the spatial relationship between IP3Rs and adenylyl cyclases.
Main Results:
- IP3Rs on sarcoplasmic reticulum augment atrial calcium transients, potentially leading to arrhythmogenesis.
- IP3-evoked calcium release stimulates adenylyl cyclases AC8 and AC1.
- AC8 co-localizes with IP3Rs, and AC1 is nearby, indicating localized signaling.
Conclusions:
- Crosstalk between calcium and cyclic AMP (cAMP) pathways occurs in atrial nanodomains.
- Similar mechanisms are observed in the sinoatrial node.
- These findings suggest novel targets for treating atrial arrhythmias.
Abstract:
Calcium handling is vital to normal physiological function in the heart. Human atrial arrhythmias, eg. atrial fibrillation, are a major morbidity and mortality burden, yet major gaps remain in our understanding of how calcium signaling pathways function and interact. Inositol trisphosphate (IP3) is a calcium-mobilizing second messenger and its agonist-induced effects have been observed in many tissue types. In the atria IP3 receptors (IR3Rs) residing on junctional sarcoplasmic reticulum augment cellular calcium transients and, when over-stimulated, lead to arrhythmogenesis. Recent studies have demonstrated that the predominant pathway for IP3 actions in atrial myocytes depends on stimulation of calcium-dependent forms of adenylyl cyclase (AC8 and AC1) by IP3-evoked calcium release from the sarcoplasmic reticulum. AC8 shows co-localisation with IP3Rs and AC1 appears to be nearby. These observations support crosstalk between calcium and cAMP pathways in nanodomains in atria. Similar mechanisms also appear to operate in the pacemaker region of the sinoatrial node. Here we discuss these significant advances in our understanding of atrial physiology and pathology, together with implications for the identification of potential novel targets and modulators for the treatment of atrial arrhythmias.
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