Suppression of store-operated calcium entry causes dilated cardiomyopathy of the heart.

Store-operated Ca entry (SOCE) is an essential Ca signaling mechanism present in most animal cells. SOCE refers to Ca influx that is activated by depletion of sarco/endoplasmic reticulum (S/ER) Ca stores. The main components of SOCE are STIM and Orai. STIM proteins function as S/ER Ca sensors, and upon S/ER Ca depletion STIM rearranges to S/ER-plasma membrane junctions and activates Orai Ca influx channels. Studies have implicated SOCE in cardiac hypertrophy pathogenesis, but SOCE's role in normal heart physiology remains poorly understood. We therefore analyzed heart-specific SOCE function in , a powerful animal model of cardiac physiology. We show that heart-specific suppression of and in larvae and adults resulted in reduced contractility consistent with dilated cardiomyopathy. Myofibers were also highly disorganized in and RNAi hearts, reflecting possible decompensation or upregulated stress signaling. Furthermore, we show that reduced heart function due to SOCE suppression adversely affected animal viability, as heart specific and RNAi animals exhibited significant delays in post-embryonic development and adults died earlier than controls. Collectively, our results demonstrate that SOCE is essential for physiological heart function, and establish as an important model for understanding the role of SOCE in cardiac pathophysiology.