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lüll Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function Parekh ABJ Physiol 2008[Jul]; 586 (13): 3043-54In eukaryotic cells, a rise in cytoplasmic Ca(2+) 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 Ca(2+) is the problem of specificity: how can Ca(2+) activate some responses but not others? We now know that the spatial profile of the Ca(2+) signal is important Ca(2+) does not simply rise uniformly throughout the cytoplasm upon stimulation but can reach very high levels locally, creating spatial gradients. The most fundamental local Ca(2+) signal is the Ca(2+) microdomain that develops rapidly near open plasmalemmal Ca(2+) channels like voltage-gated L-type (Cav1.2) and store-operated CRAC channels. Recent work has revealed that Ca(2+) 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 Ca(2+) microdomains and then describe how these highly local signals are used by Ca(2+)-permeable channels to drive cellular responses.|Animals[MESH]|Anura[MESH]|Calcium Channels/*metabolism[MESH]|Calcium Signaling[MESH]|Cell Membrane/*metabolism[MESH]|Humans[MESH]|Neurons/physiology[MESH]|Protein Structure, Tertiary[MESH] |