Store-Operated Ca²⁺ Entry and TRPC Expression; Possible Roles in Cardiac Pacemaker Tissue

Store-operated Ca²⁺ channels (SOCCs) were first identified in non-excitable cells by the observation that depletion of Ca²⁺ stores caused increased influx of extracellular Ca²⁺. Recent studies have suggested that SOCCs might be related to the transient receptor potential (TRPC) gene family. The mechanism of cardiac pacemaking involves voltage-dependent pacemaker current; in addition there is growing evidence that intracellular sarcoplasmic reticulum (SR) Ca²⁺ release plays an important role. In the present short review we assess preliminary evidence for Ca²⁺ entry related to SR store depletion and expression of TRPCs in pacemaker tissue. These newer findings suggest that Ca²⁺ entry and inward current triggered by store depletion might also contribute to the pacemaker current. Many hormones, drugs and interventions such as ischaemia and stretch, which alter Ca²⁺ handling, will also modulate pacemaker firing thought their effect on SOCCs.

Keywords: Store-operated Ca²⁺ channel, TRPC, Sinoatrial node, Heart