Abstract
ACTIVATION of intracellular Ca2+ channels by inositol 1,4,5-tris-phosphate (Ins(l,4,5)P3) represents the initial Ca2+ mobilization step in response to many extracellular signals1. Here we report that Ins(l,4,5)P3-induced channel activation in permeabilized hepatocytes is followed by a time-dependent inactivation, which is a direct consequence of ligand binding. The inactivation by Ins(l,4,5)P3 parallels the quantal character of channel opening, giving rise to a unique process of incremental inactivation whereby discrete channel populations are inhibited at each Ins(l,4,5)P3 dose. Ins(l,4,5)P3 can induce inactivation in the absence of stored Ca2+, but the inactivation rate is enhanced by increases of cytosolic Ca2+. The inhibitory effect of Ins(l,4,5)P3 can be reversed by Ins(l,4,5)P3 washout, or by chelation of cytosolic Ca2+. Thus, Ins(l,4,5)P3 and Ca2+ act as coinhibitors of the Ins(l,4,5)P3-sensitive Ca2+ channel. Inactivation is an inherent consequence of Ins(l,4,5)P3-induced channel opening which can terminate increases of cytosolic Ca2+.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Berridge, M. J. Nature 361, 315–325 (1993).
Hajnóczky, G., Gao, E., Nomura, T., Hoek, J. B. & Thomas, A. P. Biochem. J. 293, 413–422 (1993).
Renard-Rooney, D. C., Hajnóczky, G., Seitz, M. B., Schneider, T. G. & Thomas, A. P. J. biol. Chem. 268, 23601–23610 (1993).
Hajnóczky, G., Lin, C. & Thomas, A. P. J. biol. Chem. 269, 10280–10287 (1994).
Champeil, P. et al. J. biol. Chem. 264, 17665–17673 (1989).
Meyer, T. & Stryer, L. Proc. natn. Acad. Sci. U.S.A. 87, 3841–3845 (1990).
Muallem, S., Pandol, S. J. & Beeker, T. G. J. biol. Chem. 264, 205–212 (1989).
Parker, I. & Ivorra, I. Science 250, 977–979 (1990).
Oldershaw, K. A., Nunn, D. L. & Taylor, C. W. Biochem. J. 278, 705–708 (1991).
Ferris, C. D., Cameron, A. M., Huganir, R. L. & Snyder, S. H. Nature 356, 350–352 (1992).
Kindman, L. A. & Meyer, T. Biochemistry 32, 1270–1277 (1993).
Finch, E. A., Turner, T. J. & Goldin, S. M. Science 252, 443–446 (1991).
lino, M. J. gen. Physiol. 95, 1103–1122 (1990).
Bezprozvanny, I., Watras, J. & Ehrlich B. E. Nature 351, 751–754 (1991).
lino, M. & Endo, M. Nature 360, 76–78 (1992).
Marshall, I. C. B. & Taylor, C. W. J. biol. Chem. 268, 13214–13220 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hajnóczky, G., Thomas, A. The inositol trisphosphate calcium channel is inactivated by inositol trisphosphate. Nature 370, 474–477 (1994). https://doi.org/10.1038/370474a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/370474a0
This article is cited by
-
Signal transduction in mammalian oocytes during fertilization
Cell and Tissue Research (2016)
-
Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons
Nature Neuroscience (2001)
-
Temperature-dependence and conformational basis of inositol 1,4,5-trisphosphate receptor regulated by Ca2+
Science in China Series C: Life Sciences (2000)
-
Low-conductivity calcium channels in the macrophage plasma membrane: Activation by inositol-1,4,5-triphosphate
Neuroscience and Behavioral Physiology (1999)
-
Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression
Nature (1998)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.