Tissue Specificity: Store-Operated Ca²⁺ Entry in Cardiac Myocytes

Abstract

Calcium (Ca²⁺) is a key regulator of cardiomyocyte contraction. The Ca²⁺ channels, pumps, and exchangers responsible for the cyclical cytosolic Ca²⁺ signals that underlie contraction are well known. In addition to those Ca²⁺ signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca²⁺ from the extracellular milieu to the cytosol in response to depletion of intracellular Ca²⁺ stores. With non-excitable cells, this store-operated Ca²⁺ entry (SOCE) is usually easily demonstrated and is essential for prolonging cellular Ca²⁺ signaling and for refilling depleted Ca²⁺ stores. The role of SOCE in cardiomyocytes, however, is rather more elusive. While there is published evidence for increased Ca²⁺ influx into cardiomyocytes following Ca²⁺ store depletion, it has not been universally observed. Moreover, SOCE appears to be prominent in embryonic cardiomyocytes but declines with postnatal development. In contrast, there is overwhelming evidence that the molecular components of SOCE (e.g., STIM, Orai, and TRPC proteins) are expressed in cardiomyocytes from embryo to adult. Moreover, these proteins have been shown to contribute to disease conditions such as pathological hypertrophy, and reducing their expression can attenuate hypertrophic growth. It is plausible that SOCE might underlie Ca²⁺ influx into cardiomyocytes and may have important signaling functions perhaps by activating local Ca²⁺-sensitive processes. However, the STIM, Orai, and TRPC proteins appear to cooperate with multiple protein partners in signaling complexes. It is therefore possible that some of their signaling activities are not mediated by Ca²⁺ influx signals, but by protein-protein interactions.