Cytosolic Ca2+ domain-dependent protective action of adenosine in cardiomyocytes

Area of Science:

• Cardiology
• Cell Physiology
• Calcium Signaling

Background:

• Heterogeneous spatiotemporal patterns of cytosolic Ca2+ are observed in beating cardiac cells and linked to contraction.
• Spatial heterogeneity of intracellular Ca2+ in non-beating cardiomyocytes is known, but its functional role in resting cells is unclear.

Purpose of the Study:

• To investigate the functional implications of spatial heterogeneity of intracellular Ca2+ distribution in resting cardiomyocytes.
• To determine if adenosine's protective effects are uniform across different intracellular Ca2+ domains.

Main Methods:

• Utilized epifluorescent digital imaging to visualize distinct cytosolic Ca2+ domains in single, non-beating, fluo-3-loaded cardiomyocytes.
• Applied extracellular K+ (16 mM) to induce Ca2+ loading and observed the effects of adenosine (1 mM) on this response.

Main Results:

• Distinct domains of lower (0.17 microM) and higher (0.37 microM) basal cytosolic Ca2+ concentrations were identified.
• Extracellular K+ uniformly increased cytosolic Ca2+ across all domains.
• Adenosine selectively inhibited K+-induced Ca2+ loading in lower basal Ca2+ domains, but not in higher basal Ca2+ domains.

Conclusions:

• The response to adenosine's protective action is heterogeneous within a single resting cardiomyocyte.
• Basal Ca2+ concentration within a cytosolic domain dictates adenosine's domain-specific cytoprotective effect.