1. As previously reported, in hippocampal slices from Sprague-Dawley rats, 13-min applications of 2-deoxy-D-glucose (2-DG) (substituting 10 mM 2-DG for glucose)-which sharply depress field excitatory postsynaptic potentials (EPSPs)-are followed by a sustained potentiation of the initial slopes of EPSPs (2-DG-LTP). 2. Such 2-DG-LTP is not prevented by exposing slices to Ca(2+)-free medium for 25 min before the 13-min 2-DG applications (in Ca(2+)-free medium). Therefore 2-DG-LTP is not dependent on influx of external Ca2+ during the 2-DG applications. 3. When the Ca(2+)-free conditions begin 15 min before, and are maintained for 10 min after, the 13-min 2-DG applications (in Ca(2+)-free medium), 2-DG-LTP is either totally suppressed or much reduced. A delayed Ca2+ influx thus plays a crucial role in the induction of 2-DG-LTP. 4. Much longer Ca(2+)-free pretreatment (for 77 min) largely abolishes 2-DG-LTP. Therefore Ca2+ release from a compartment (presumably intracellular) that is not readily depleted is also important for the induction of 2-DG-LTP. 5. This intracellular Ca2+ store is sensitive to dantrolene sodium (10 microM)-which prevents 2-DG-LTP-but not 10 microM thapsigargin. 2-DG-LTP of isolated N-methyl-D-aspartate-receptor-mediated EPSPs is only partly reduced by dantrolene. 6. Dantrolene (10 microM) also reduces or abolishes posttetanic potentiation, but not paired-pulse facilitation. 7. Depotentiation by 1-Hz stimulation is abolished by 20 microM dantrolene. 8. In contrast to the above, long-term potentiation (LTP) elicited by tetanic stimulation is prevented by 10 microM thapsigargin but not by dantrolene (< or = 50 microM). 9. In conclusion, two mechanisms of intracellular Ca2+ concentration increase appear to be essential for LTP induction by 2-DG. One is Ca2+ influx after the 2-DG application; the other is Ca2+ release from a dantrolene-sensitive internal store. The opposite effects of thapsigargin and dantrolene on 2-DG-LTP and tetanic LTP suggest that distinct internal sources of Ca2+ may be needed for the induction of these two forms of LTP.
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