STIM1 Increases Ca2+ Stores in the Sarcoplasmic Reticulum of Adult Feline Ventricular Myocytes

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STIM1 is a Sarcoplasmic Reticulum (SR) membrane resident protein implicated in sensing and maintaining SR Ca2+ levels. The role of STIM1 in the regulation of SR Ca2+ stores in the normal and diseased heart is not well described. Our data shows that STIM1 is present at low levels in adult normal cardiac myocytes, but expression levels increase after cardiac injury. Because STIM1 is involved in regulating intracellular Ca2+ homeostasis, we hypothesize that increased STIM1 expression after cardiac injury may be involved in the disturbed Ca2+ cycling within diseased cardiomyocytes. Using cultured adult ventricular feline myocytes, we found that adenoviral vector mediated overexpression of STIM1 induces cell death in 80% of myocytes versus only 5% in uninfected controls. We also showed that rested state contractions were minimally increased in unpaced STIM1 overexpressing myocytes, compared with control myocytes (3 fold increase), suggesting that STIM increases SR Ca2+ stores under conditions in which SR Ca2+ stores are usually depleted. STIM1 overexpressing myocytes had increased Ca2+ transient peaks (measured with fluo-4) as well as increased contractions. We are currently exploring how STIM1 modifies SR load and mechanisms by which STIM1 alters excitation-contraction coupling. Our findings show that STIM1 can increase SR Ca2+ loading and this could have effects on contractility and arrhythmias in disease.