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Biophysical Journal 68: 2601-2607 (1995)
© 1995 the Biophysical Society

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Kinetics of cytosolic Ca2+ concentration after photolytic release of 1-D-myo-inositol 1,4-bisphosphate 5-phosphorothioate from a caged derivative in guinea pig hepatocytes.

J F Wootton, J E Corrie, T Capiod, J Feeney, D R Trentham and D C Ogden

National Institute for Medical Research, London, United Kingdom.

ABSTRACT

The influence of 1-D-myo-inositol 1,4,5-trisphosphate (InsP3) breakdown by InsP3 5-phosphatase in determining the time course of Ca2+ release from intracellular stores was investigated with flash photolytic release of a stable InsP3 derivative, 5-thio-InsP3, from a photolabile caged precursor. The potency and Ca(2+)-releasing properties of the biologically active D isomers of 5-thio-InsP3 and InsP3 itself were compared by photolytic release in guinea pig hepatocytes. After a light flash, cytosolic free calcium concentration ([Ca2+]i) showed an initial delay before rising quickly to a peak and declining more slowly to resting levels, with time course and amplitude generally similar to those seen with photolytic release of InsP3. Differences were a three- to eightfold lower potency of 5-thio-InsP3 in producing Ca2+ release, much longer delays between photolytic release and Ca2+ efflux with low concentrations of 5-thio-InsP3 than with InsP3, and persistent reactivation of Ca2+ release, producing periodic fluctuations of cytosolic [Ca2+]i with high concentrations of 5-thio-InsP3 but not InsP3 itself. The lower potency of 5-thio-InsP3 may be a result of a lower affinity for closed receptor/channels or a lower open probability of liganded receptor/channels. The longer delays with 5-thio-InsP3 at low concentration suggest that metabolism of InsP3 by 5-phosphatase may reduce the concentration sufficiently to prevent receptor activation and may have a similar effect on InsP3 concentration during hormonal activation.(ABSTRACT TRUNCATED AT 250 WORDS)




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G. Guihard, J. Noel, and T. Capiod
Ca2+ Depletion and Inositol 1,4,5-Trisphosphate-evoked Activation of Ca2+ Entry in Single Guinea Pig Hepatocytes
J. Biol. Chem., April 28, 2000; 275(18): 13411 - 13414.
[Abstract] [Full Text] [PDF]


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Copyright © 1995 by the Biophysical Society.