Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase (original) (raw)
- Letter
- Published: 19 May 1994
Nature volume 369, pages 235–239 (1994)Cite this article
- 521 Accesses
- 428 Citations
- 3 Altmetric
- Metrics details
Abstract
PROTEIN kinases modulate the activity of several ligand-gated ion channels1, including the NMDA (_N_-methyl-D-aspartate)2 subtype of glutamate receptor. Although phosphorylation and dephosphorylation of glutamate receptors may participate in several lasting physiological and pathological alterations of neuronal excitability3–7, the physiological control of this cycle for NMDA channels has not yet been established. Using cell-attached recordings in acutely dissociated adult rat dentate gyrus granule cells, we now demonstrate that inhibitors of an endogenous serine/threonine phosphatase prolong the duration of single NMDA channel openings, bursts, clusters and superclusters. Okadaic acid, a non-selective phosphatase inhibitor, prolongs channel openings only at a concentration that inhibits the Ca2+/calmodulin-dependent phosphatase 2B (calcineurin)8, and is ineffective when Ca2+ entry through NMDA channels is prevented. Furthermore, FK506, an inhibitor of calcineurin9,10, mimics the effects of okadaic acid. Thus in adult neurons, calcineurin, activated by calcium entry through native NMDA channels, shortens the duration of channel openings. Simulated synaptic currents11 were enhanced after phosphatase inhibition, which is consistent with the importance of phosphorylation of the NMDA-receptor complex in the short- and long-term control of neuronal excitability.
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 SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Similar content being viewed by others
References
- Raymond, L. A., Blackstone, C. D. & Huganir, R. L. Trends Neurosci. 16, 147–153 (1993).
Article CAS Google Scholar - Chen, L. & Huang, L.-Y. M. Nature 356, 521–523 (1992).
Article ADS CAS Google Scholar - Bliss, T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).
Article ADS CAS Google Scholar - Köhr, G., De Koninck, Y. & Mody, I. J. Neurosci. 13, 3612–3627 (1993).
Article Google Scholar - Figurov, A., Boddeke, H. & Muller, D. Eur. J. Neurosci. 5, 1035–1041 (1993).
Article CAS Google Scholar - Mulkey, R. M., Herron, C. E. & Malenka, R. C. Science 261, 1051–1055 (1993).
Article ADS CAS Google Scholar - Tingley, W. G., Roche, K. W., Thompson, A. K. & Huganir, R. L. Nature 364, 70–73 (1993).
Article ADS CAS Google Scholar - Bialojan, C. & Takai, A. J. Biochem. 256, 283–290 (1988).
Article CAS Google Scholar - Liu, J. et al. Cell 66, 807–815 (1991).
Article CAS Google Scholar - Clipstone, N. A. & Crabtree, G. R. Nature 357, 695–697 (1992).
Article ADS CAS Google Scholar - Edmonds, B. & Colquhoun, D. Proc. R. Soc. 250, 279–286 (1992).
Article ADS CAS Google Scholar - MacDonald, J. F., Mody, I. & Salter, M. W. J. Physiol., Lond. 414, 17–34 (1989).
Article CAS Google Scholar - Gibb, A. J. & Colquhoun, D. J. Physiol., Lond. 456, 143–179 (1992).
Article CAS Google Scholar - Haystead, T. A. J. et al. Nature 337, 78–81 (1989).
Article ADS CAS Google Scholar - Abdul-Ghani, M., Kravitz, E. A., Meiri, H. & Rahamimoff, R. Proc. natn. Acad. Sci. U.S.A. 88, 1803–1807 (1991).
Article ADS CAS Google Scholar - Sah, P., Hestrin, S. & Nicoll, R. A. Science 246, 815–818 (1989).
Article ADS CAS Google Scholar - Mayer, M. L. & Westbrook, G. L. J Physiol., Lond. 394, 501–527 (1987).
Article CAS Google Scholar - Schneggenburger, R., Zhou, Z., Konnerth, A. & Neher, E. Neuron 11, 133–143 (1993).
Article CAS Google Scholar - Legendre, P., Rosenmund, C. & Westbrook, G. L. J. Neurosci. 13, 674–684 (1993).
Article CAS Google Scholar - Rosenmund, C. & Wesbrook, C. L. Neuron 10, 805–614 (1993).
Article CAS Google Scholar - Nowak, L., Bregestovski, P., Ascher, P., Herbert, A. & Prochiantz, A. Nature 307, 462–465 (1984).
Article ADS CAS Google Scholar - Klee, C. B., Draetta, G. F. & Hubbard, M. J. Adv. Enzym. 61, 149–200 (1988).
CAS Google Scholar - Steiner, J. P. et al. Nature 358, 584–587 (1992).
Article ADS CAS Google Scholar - Halpain, S. & Greengard, P. Neuron 5, 237–246 (1990).
Article CAS Google Scholar - Goto, S. et al. J. Neurochem. 45, 276–283 (1985).
Article CAS Google Scholar - Polli, J. W., Billingsley, M. L. & Kincaid, R. L. Devl Brain Res. 63, 105–119 (1991).
Article CAS Google Scholar - Watanabe, M., Inoue, Y., Sakimura, K. & Mishina, M. Neuroreport 3, 1138–1140 (1992).
Article CAS Google Scholar - Morioka, M. et al. J. Neurochem. 58, 1798–1809 (1992).
Article CAS Google Scholar - Crepel, V., Hammond, C., Krnjevic, K., Chinestra, P. & Ben-Ari, Y. J. Neurophys. 69, 1774–1778 (1993).
Article CAS Google Scholar - Lester, R. A. J. & Jahr, C. E. J. Neurosci. 12, 635–643 (1992).
Article CAS Google Scholar
Author information
Author notes
- Istvan Mody: To whom correspondence should be addressed.
Authors and Affiliations
- Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, California, 94305, USA
David N. Lieberman - Department of Anesthesiology and Pain Management, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75235-9068, USA
Istvan Mody
Authors
- David N. Lieberman
You can also search for this author inPubMed Google Scholar - Istvan Mody
You can also search for this author inPubMed Google Scholar
Rights and permissions
About this article
Cite this article
Lieberman, D., Mody, I. Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase.Nature 369, 235–239 (1994). https://doi.org/10.1038/369235a0
- Received: 26 August 1993
- Accepted: 05 May 1994
- Issue Date: 19 May 1994
- DOI: https://doi.org/10.1038/369235a0