Compartmentalized cAMP signalling is important in the regulation of Ca2+ cycling in the heart

Co-ordinated myocyte handling of calcium is essential for efficient excitation-contraction coupling in the heart. The calcium cycling activity can be modulated by adrenergic stimulation and subsequent phosphorylation. Important functional consequences of phosphorylation include a greater influx of calcium through the voltage-dependent L-type Ca2+ channel and a greater release of calcium from SR (sarcoplasmic reticulum) through the ryanodine R-2 receptor. Furthermore, a more efficient reuptake through SERCA2 (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 2) is a result of phosphorylation of its regulatory protein phospholamban. Compartmentalized signalling is important in this signalling cascade, and A-kinase-anchoring proteins play a central role by providing a high level of specificity.