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In CTLs: High glucose-culture enhances thapsigargin-induced SOCE but decreases target recognition-induced Ca2+ influx. High glucose-culture regulates expression of ORAIs and STIMs without affecting glucose uptake. More high glucose-cultured CTLs are prone to necrosis after execution of killing.

Mammalian inner hair cells (IHCs) transduce sound into depolarization and transmitter release. Big conductance and voltage- and Ca2+-activated K+ (BK) channels are responsible for fast membrane rep...

Store-operatedCa 2+ entry(SOCE)isawidespreadmechanismincellstoraisecytosolic Ca 2+ and to refill Ca 2+ stores. T cells critically rely on SOCE mediated by stromal interaction molecules (STIM) and Orai molecules for their activation and regulation of gene transcription; cells such as muscle cells, neurons or melanocytes probably utilize SOCE for the transmission of inducible receptor-mediated function as well as for generalized Ca 2+ homeostasis mechanisms. Exposure to environmental or cell-intrinisic reactive oxygen species (ROS) can affect several components involved in Ca 2+ homeostasis and thus alter multiple pathways. While all cells have a capacity to produce intracellular ROS, exposure of immune and skin cells to extracellular oxidative stress is particularly high during inflammation and/or with UV exposure. This review brieflysummarizescell-intrinsicsourcesofROSandfocusesoncurrentfindingsandcontroversies regarding the regulation of STIM and Orai by oxidative modifications. We also introduce melanocytes as a new model system to study the function of STIM and Orai isoforms under physiological conditions that include exposure to UV light as an activating stimulus.

Cell polarization enables restriction of signalling into microdomains. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T-cell activation. Here, we analyse calcium microdomains at the IS with total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signal following IS formation is sufficiently low to prevent calcium-dependent inactivation of ORAI channels. This is achieved by localizing mitochondria close to ORAI channels. Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re-distributed into areas beneath mitochondria, which prevented PMCA up-modulation and decreased calcium export locally. This nano-scale distribution—only induced following IS formation—maximizes the efficiency of calcium influx through ORAI channels while it decreases calcium clearance by PMCA, resulting in a more sustained NFAT activity and subsequent activation of T cells.