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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chetkovich, D. M. Gray, R. Johnston, D. Sweatt, J. D. |
| Description | Author Affiliation: Chetkovich DM ( Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030.); |
| Abstract | Tetanic stimulation of the Schaffer collateral inputs into area CA1 of the hippocampus causes N-methyl-D-aspartate (NMDA) receptor activation, an effect that contributes to the induction of long-term potentiation (LTP) in this region. The present studies demonstrate that LTP-inducing tetanic stimulation in rat hippocampal area CA1 elicited increased levels of cAMP. The elevation of cAMP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). Bath application of NMDA also resulted in an increase in cAMP in CA1, an effect that was blocked by both APV and removal of extracellular Ca2+. These findings suggest that activation of NMDA receptors elicits a Ca(2+)-dependent increase in cAMP, and taken together with the data from tetanic stimulation, suggest that NMDA-receptor-mediated increases in cAMP could play a role in the induction of LTP in area CA1. One role for cAMP may be to increase Ca2+ influx through voltage-gated Ca2+ channels, as it was observed that application of either 8-bromo-cAMP or NMDA increased the fractional open time of high-threshold Ca2+ channels in CA1 pyramidal cells. Our results raise the possibility that a positive-feedback loop for Ca2+ influx in area CA1 exists. In this model, NMDA receptor-mediated Ca2+ influx leads to an enhancement of further Ca2+ influx via intermediate steps of increased cAMP and subsequent increased voltage-gated Ca2+ channel activity. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 88 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1991-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 2-Amino-5-phosphonovalerate Pharmacology 8-Bromo Cyclic Adenosine Monophosphate Calcium Channels Physiology Cyclic AMP Metabolism Hippocampus N-Methylaspartate Receptors, N-Methyl-D-Aspartate Animals Calcium Drug Effects Egtazic Acid Electric Stimulation Glutamates Glutamic Acid In Vitro Techniques Membrane Potentials Rats, Inbred Strains Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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