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

Abstract

Calcium (Ca) is a key regulator of cardiomyocyte contraction. The Ca channels, pumps, and exchangers responsible for the cyclical cytosolic Ca signals that underlie contraction are well known. In addition to those Ca signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca from the extracellular milieu to the cytosol in response to depletion of intracellular Ca stores. With non-excitable cells, this store-operated Ca entry (SOCE) is usually easily demonstrated and is essential for prolonging cellular Ca signaling and for refilling depleted Ca stores. The role of SOCE in cardiomyocytes, however, is rather more elusive. While there is published evidence for increased Ca influx into cardiomyocytes following Ca 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 Ca influx into cardiomyocytes and may have important signaling functions perhaps by activating local Ca-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 Ca influx signals, but by protein-protein interactions.

Creating a New Cancer Therapeutic Agent by Targeting the Interaction between Bcl-2 and IP3Receptors

“…It is unclear what mechanism underlies the influx of Ca 2+ during BIRD-2-induced cell death. In most cells, depletion of ER Ca 2+ content activates a "store-operated Ca 2+ entry" (SOCE) mechanism to allow replenishment (Putney 2007;Bodnar et al 2017;Bootman and Rietdorf 2017;Putney et al 2017). However, knockdown of the SOCE component STIM1, or addition of pharmacological inhibitors, did not protect against BIRD-2-induced apoptosis (Bittremieux et al 2018b).…”

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

“…The relevance of SOCE for excitation-contraction coupling in healthy adult cardiac myocytes is still controversial [13,14]. SOCE has been shown to be present in neonatal rat cardiac myocytes but hardly detectable in healthy adult cardiac myocytes, and re-emerges during states of increased cardiac stress [14,15]. Growing evidence suggests that pressure-overload (thoracic aortic constriction and abdominal aortic banding) and exposure to phenylephrine or angiotensin II results in stimulation of SOCE and SOC channels, which may be important for development of ventricular hypertrophy by triggering calcineurin-NFAT-signaling in rat cardiomyocytes [16,17].…”

The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

“…Meanwhile, its reduction in the cytosol is due to the reuptake of Ca 2+ by SERCA in the SR or the activity of Na + /Ca 2+ exchanger (NCX) located in the PM (Bers, 2002 ). The presence of SOCE in cardiomyocytes has been initially ignored since cardiomyocytes have large Ca 2+ influx arising with each heartbeat (Collins et al, 2013 ; Bootman and Rietdorf, 2017 ). Actually, the contribution of SOCE to normal cardiac physiology is still under debate (Bootman and Rietdorf, 2017 ).…”

“…The presence of SOCE in cardiomyocytes has been initially ignored since cardiomyocytes have large Ca 2+ influx arising with each heartbeat (Collins et al, 2013 ; Bootman and Rietdorf, 2017 ). Actually, the contribution of SOCE to normal cardiac physiology is still under debate (Bootman and Rietdorf, 2017 ). However, growing set of experiments have demonstrated the presence of SOCE especially in neonatal cardiomyocytes (Bartoli and Sabourin, 2017 ).…”