Calcium dependence of LTP induced by 2-deoxyglucose in CA1 neurons

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 Ca²⁺free medium for 25 min before the 13-min 2-DG applications (in Ca²⁺-free medium). Therefore 2-DG-LTP is not dependent on influx of external Ca²⁺ during the 2-DG applications. 3. When the Ca²⁺ free conditions begin 15 min before, and are maintained for 10 min after, the 13 min 2-DG applications (in Ca²⁺-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 Ca²⁺ 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 μM)-which prevents 2-DG-LTP but not 10 μM thapsigargin. 2-DG-LTP of isolated N-methyl-D-aspartate-receptor-mediated EPSPs is only partly reduced by dantrolene. 6. Dantrolene (10 μM) also reduces or abolishes posttetanic potentiation, but not paired pulse facilitation. 7. Depotentiation by 1-Hz stimulation is abolished by 20 μM dantrolene. 8. In contrast to the above, long-term potentiation (LTP) elicited by tetanic stimulation is prevented by 10 μm thapsigargin but not by dantrolene (≤50 μM). 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.