SOCE and STIM1 signaling in the heart: Timing and location matter

Store operated Ca²⁺ entry (SOCE) is an ancient and ubiquitous Ca²⁺ signaling pathway discovered decades ago, but the function of SOCE in human physiology is only now being revealed. The relevance of this pathway to striated muscle was solidified with the description of skeletal myopathies that result from mutations in STIM1 and Orai1, the two SOCE components. Here, we consider the evidence for STIM1 and SOCE in cardiac muscle and the sinoatrial node. We highlight recent studies revealing a role for STIM1 in cardiac growth in response to developmental and pathologic cues. We also review the role of STIM1 in the regulation of SOCE and Ca²⁺ store refilling in a non-Orai dependent manner. Finally, we discuss the importance of this pathway in ventricular cardiomyocytes where SOCE contribute to developmental growth and in pacemaker cells where SOCE likely has a fundamental to generating the cardiac rhythm.