Numerical modeling calcium and CaMKII effects in the SA node

Sinoatrial node (SAN) is the primary heart pacemaker which initiates each heartbeat under normal conditions. Numerous experimental data have demonstrated that Ca²⁺- and CaMKII-dependent processes are crucially important for regulation of SAN cells. However, specific mechanisms of this regulation and their relative contribution to pacemaker function remain mainly unknown. Our review summarizes available data and existing numerical modeling approaches to understand Ca²⁺ and CaMKII effects on the SAN. Data interpretation and future directions to address the problem are given within the coupled-clock theory, i.e., a modern view on the cardiac pacemaker cell function generated by a system of sarcolemmal and intracellular proteins.