期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 586, 期 13, 页码 3043-3054出版社
WILEY
DOI: 10.1113/jphysiol.2008.153460
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资金
- British Heart Foundation Funding Source: Medline
- Medical Research Council [G0200218] Funding Source: Medline
- Medical Research Council [G0200218] Funding Source: researchfish
- MRC [G0200218] Funding Source: UKRI
In eukaryotic cells, a rise in cytoplasmic Ca2+ can activate a plethora of responses that operate on time scales ranging from milliseconds to days. Inherent to the use of a promiscuous signal like Ca2+ is the problem of specificity: how can Ca2+ activate some responses but not others ? We now know that the spatial profile of the Ca2+ signal is important Ca2+ does not simply rise uniformly throughout the cytoplasm upon stimulation but can reach very high levels locally, creating spatial gradients. The most fundamental local Ca2+ signal is the Ca2+ microdomain that develops rapidly near open plasmalemmal Ca2+ channels like voltage-gated L-type (Cav1.2) and store-operated CRAC channels. Recent work has revealed that Ca2+ microdomains arising from these channels are remarkably versatile in triggering a range of responses that differ enormously in both temporal and spatial profile. Here, I delineate basic features of Ca2+ microdomains and then describe how these highly local signals are used by Ca2+-permeable channels to drive cellular responses.
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