Our understanding of cardiac Ca2+ signaling and the molecular mechanisms of excitation-contraction coupling (EC-coupling) has been revolutionized by the visualization of intracellular and subcellular Ca2+ release events (microdomain Ca2+) with laser-scanning confocal microscopy and the use of specific fluorescent Ca2+ indicators. In the heart, the leading mechanism of intracellular Ca2+ release is Ca2+-induced Ca2+ release (CICR) via sarcoplasmic reticulum (SR) release channels (ryanodine receptors, RyRs), which is a prerequisite for muscle contraction. A second mechanism, Ca2+ release through channels sensitive to the intracellular second messenger inositol-1,4,5-triphosphate (InsP3) has been described, predominantly in atrial myocytes. Its contribution and significance in cardiac EC-coupling as well as in excitation-transcription coupling is still a matter of debate. The spatial and temporal characteristics of local IP3 mediated Ca2+ release events (Ca2+ puffs) in atrial myocytes are distinctive from RyR SR-Ca2+ release events (Ca2+ sparks) and exhibit some similarities with non-excitable cells. However, there is preliminary evidence suggesting that this type of Ca2+ signaling plays a role in cellular remodeling associated with atrial disease and may contribute to the frequent and clinically relevant arrhythmias. The potential clinical relevance and significance of InsP3-generated stimuli in various cardiac pathologies emphasizes the need to understand how InsP3 may participate in normal EC-coupling and under pathophysiological situations. This is examined in our team on cellular and subcellular level in acute cell preparations by using Ca2+ imaging with laser-scanning confocal microscopy, UV-laser flash and two-photon excitation photolysis of caged compounds and patch-clamp techniques in combination with cardiac disease models (transgenic mouse models).
