Selective ablation of the long splice variant of STIM1 inhibits SOCE, prevents cardiac hypertrophy, and causes severe cardiac impairment and premature death in exercised mice

Abstract

Stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca entry (SOCE), has been suggested to be a mediator of the myocardial hypertrophic response in heart disease. However, its contribution to cardiac hypertrophy and whether STIM1 (and SOCE) plays an adaptive or maladaptive role remain controversial. In cardiomyocytes, STIM1 is present as two splice variants: a short form (STIM1S), and a long form (STIM1L). The functional properties and the relative roles of these two STIM1 variants are unknown.