Atrial excitation-contraction coupling (ECC) and pacemaker activity are both dependent on intracellular calcium (Ca2+) cycling, and alterations in Ca2+ cycling are strongly implicated in the pathophysiology of atrial fibrillation (AF). Depolarization of cardiac myocytes promotes Ca2+ influx via L-type calcium channels (LTCCs), which then releases a larger quantity of Ca2+ from intracellular stores. For ECC, elevated Ca2+ interacts with troponin C, promoting cross bridge interaction and myocyte contraction. Relaxation during diastole requires intracellular Ca2+ levels to return to baseline levels, either via reuptake of Ca2+ into the sarcoplasmic reticulum or extrusion from the cell by the sodium calcium exchanger. In pacemaking cells, Ca2+ influx via the LTCC underlies the upstroke of the action potential; Ca2+ (and sodium) influx via HCN (hyperpolarization-activated cyclic nucleotide-gated) channels regulates the rate of diastolic depolarization.