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 R2 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.