CALCIUM-DEPENDENCE OF LTP INDUCED BY 2-DEOXYGLUCOSE IN CA1 NEURONS.
TEKKoK, S. and K. KRNJEVI.
Anaesthesia Research and Physiology Departments, McGill University,
Montr[acute]eal, QC, H3G 1Y6, Canada.
APStracts 3:0151N, 1996.
SUMMARY AND CONCLUSIONS
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 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ release
from a compartment (presumably intracellular) that is not readily depleted is
also important for the induction of 2-DG-LTP. 5. This intracellular Ca 2+
store is sensitive to dantrolene Na (10 [mu]M) -- which prevents 2-DG-LTP -
but not 10 [mu]M thapsigargin. 2-DG-LTP of isolated NMDA receptor-mediated
EPSPs is only partly reduced by dantrolene. 6. Dantrolene (10 [mu]M) also
reduces or abolishes post-tetanic potentiation, but not paired-pulse
facilitation. 7. Depotentiation by 1 Hz stimulation is abolished by 20 [mu]M
dantrolene. 8. In contrast to item 5, LTP elicited by tetanic stimulation is
prevented by 10 [mu]M thapsigargin but not by dantrolene (= 50 [mu]M). 9. In
conclusion, two mechanisms of [Ca 2+ ] i increase appear to be essential for
LTP induction by 2-DG. One is Ca 2+ influx after the 2-DG application; the
other, Ca 2+ 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 Ca 2+ may be needed for the induction of
these two forms of LTP.
Received 21 March 1996; accepted in final form 24 June 1996.
APS Manuscript Number J232-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996