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The coupling of plasma membrane calcium entry to calcium uptake by endoplasmic reticulum and mitochondria
Author(s) -
GarcíaSancho Javier
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.255661
Subject(s) - endoplasmic reticulum , serca , microbiology and biotechnology , exocytosis , uniporter , cytosol , organelle , calcium signaling , mitochondrion , plasma membrane ca2+ atpase , calcium , chemistry , stim1 , voltage dependent calcium channel , biophysics , biology , biochemistry , secretion , signal transduction , atpase , organic chemistry , enzyme
Key points Cross‐talk between organelles and plasma membrane Ca 2+ channels modulates cytosolic Ca 2+ signals in different ways. In chromaffin cells Ca 2+ entry through voltage‐operated channels is amplified by Ca 2+ release from the endoplasmic reticulum (ER) and generates subplasmalemmal high Ca 2+ microdomains (HCMDs) as high as 20–50 μ m , which trigger exocytosis. Subplasmalemmal mitochondria take up Ca 2+ from HCMDs and avoid progression of the Ca 2+ wave towards the cell core. In non‐excitable HEK293 cells activation of store‐operated Ca 2+ entry triggered by ER Ca 2+ emptying also generates subplasmalemmal HCMDs of about 2 μ m . In this case most of the Ca 2+ is taken up by the ER rather than by mitochondria. This outcome may be explained because sarco‐endoplasmic reticulum Ca 2+ ATPase (SERCA) has much higher Ca 2+ affinity than mitochondria. The relative positioning of organelles, channels and accessory proteins may also play a role.Abstract Cross‐talk between organelles and plasma membrane Ca 2+ channels is essential for modulation of the cytosolic Ca 2+ ([Ca 2+ ] C ) signals, but such modulation may differ among cells. In chromaffin cells Ca 2+ entry through voltage‐operated channels induces calcium release from the endoplasmic reticulum (ER) that amplifies the signal. [Ca 2+ ] C microdomains as high as 20–50 μ m are sensed by subplasmalemmal mitochondria, which accumulate large amounts of Ca 2+ through the mitochondrial Ca 2+ uniporter (MCU). Mitochondria confine the high‐Ca 2+ microdomains (HCMDs) to beneath the plasma membrane, where exocytosis of secretory vesicles happens. Cell core [Ca 2+ ] C is much smaller (1–2 μ m ). By acting as a Ca 2+ sink, mitochondria stabilise the HCMD in space and time. In non‐excitable HEK293 cells, activation of store‐operated Ca 2+ entry, triggered by ER Ca 2+ emptying, also generated subplasmalemmal HCMDs, but, in this case, most of the Ca 2+ was taken up by the ER rather than by mitochondria. The smaller size of the [Ca 2+ ] C peak in this case (about 2 μ m ) may contribute to this outcome, as the sarco‐endoplasmic reticulum Ca 2+ ATPase has much higher Ca 2+ affinity than MCU. It is also possible that the relative positioning of organelles, channels and effectors, as well as cytoskeleton and accessory proteins plays an important role.