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Science 29 April 1988:
Vol. 240. no. 4852, pp. 653 - 656
DOI: 10.1126/science.2452482

Articles

Science, Vol 240, Issue 4852, 653-656
Copyright © 1988 by American Association for the Advancement of Science


articles

Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate

T Meyer, D Holowka, and L Stryer

Department of Cell Biology, Sherman Fairchild Center, Stanford University School of Medicine, CA 94305.

The kinetics of calcium release by inositol 1,4,5-trisphosphate (IP3) in permeabilized rat basophilic leukemia cells were studied to obtain insight into the molecular mechanism of action of this intracellular messenger of the phosphoinositide cascade. Calcium release from intracellular storage sites was monitored with fura-2, a fluorescent indicator. The dependence of the rate of calcium release on the concentration of added IP3 in the 4 to 40 nM range showed that channel opening requires the binding of at least three molecules of IP3. Channel opening occurred in the absence of added adenosine triphosphate, indicating that IP3 acts directly on the channel or on a protein that gates it. The channels were opened by IP3 in less than 4 seconds. The highly cooperative opening of calcium channels by nanomolar concentrations of IP3 enables cells to detect and amplify very small changes in the concentration of this messenger in response to hormonal, sensory, and growth control stimuli.


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