Abstract
The archetypal store-operated Ca2+ channels (SOCs), Orai1, which are stimulated by the endo/sarcoplasmic reticulum (ER/SR) Ca2+ sensor stromal interaction molecule 1 (STIM1) upon Ca2+ store depletion is traditionally viewed as instrumental for the function of non-excitable cells. In the recent years, expression and function of Orai1 have gained recognition in excitable cardiomyocytes, albeit controversial. Even if its cardiac physiological role in adult is still elusive and needs to be clarified, Orai1 contribution in cardiac diseases such as cardiac hypertrophy and heart failure (HF) is increasingly recognized. The present review surveys our current arising knowledge on the new role of Orai1 channels in the heart and debates on its participation to cardiac hypertrophy and HF.
Highlights
Spatiotemporal modulation of intracellular Ca2+ levels provides a signal transduction mechanism in virtually all cell types
The notion of store-operated Ca2+ entry (SOCE) was first proposed in salivary gland cells as a “capacitative Ca2+ entry” (Putney, 1986, 1990), which couples the extracellular Ca2+ influx to the depletion of endoplasmic reticulum (ER) Ca2+ stores
The modern molecular period identifies two essentials molecular candidates responsible for the SOCE and the ICRAC: one is the stromal interaction molecule 1 (STIM1) protein, serving as an ER Ca2+ sensor via its N-terminal EF-hand domain; the second is Orai1 forming the classical store-operated Ca2+ channels (SOCs), which is highly selective for Ca2+
Summary
Spatiotemporal modulation of intracellular Ca2+ levels provides a signal transduction mechanism in virtually all cell types This is used to determine which both short- and long-term cellular functions are activated and when. This fine control of Ca2+ handling is notably setup by various ion channels at the plasma membrane, including the store-operated Ca2+ channels (SOCs) and their corresponding store-operated Ca2+ entry (SOCE). ICRAC was described as a sustained non-voltage-activated Ca2+ inward current with an inward rectification positive to reversal potential. It is highly selective for Ca2+ ions over Ba2+, Sr2+, and Mn2+ (Hoth and Penner, 1992).
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