Spatio-temporal distribution of intracellular calcium transients during
epileptiform activity in guinea pig hippocampal slices.
Albowitz, B., P. Knig, U. Kuhnt.
Neurobiological Laboratories, Max-Planck-Institute for Biophysical
Chemistry, Gttingen, Germany, Institute for Experimental Epilepsy Research,
University of Mnster, Mnster, Germany.
APStracts 3:0211N, 1996.
Calcium ions are known to play an important role in epileptogenesis. While
there is clear evidence for increased neuronal calcium influx during
epileptiform potentials, direct measurements of the corresponding
intracellular calcium transients are rare and the origin of calcium influx is
not known. Therefore, the spatial and temporal distribution of intracellular
calcium transients during epileptiform activity in guinea pig hippocampal
slices was monitored using the indicator Calcium-Green and a fast optical
recording method. Two models of epilepsy (bicuculline and low Mg 2+ ) were
compared. In both models, single epileptiform events were evoked by electrical
stimulation of the Schaffer collaterals in CA1 or of stratum pyramidale in
area CA3. Intracellular calcium transients during epileptiform activity were
about five times larger than during control stimulation. Calcium transients
during epileptiform activity were present across at least the entire CA1 area,
whereas presynaptic calcium transients from stimulated fibres were only seen
at a distance up to 1mm from the stimulation site. DL-2-amino-5-
phosphonovaleric acid (APV), a specific antagonist of the NMDA receptor,
abolished low Mg 2+ epileptiform activity and reduced bicuculline induced
epileptiform activity; it reduced calcium transients following stimulation of
CA1 by only 29% (bicuculline) and 38% (low Mg 2+ ). For comparison, calcium
transients during control stimulation were 78% (bicuculline) and 69% (low Mg
2+ ) smaller than epileptiform calcium transients. At a distance from the
stimulation site, calcium transients and their NMDA receptor dependent
components were largest in stratum pyramidale in the bicuculline model and in
stratum oriens in the low Mg 2+ model. In both models, minimal onset latencies
of calcium influx shifted with increasing distance to the stimulation
electrode from stratum radiatum to stratum oriens. APV reduced the extent of
spread of calcium transients in the low Mg 2+ model. In the bicuculline model,
the spatial extent of spread of epileptiform calcium transients was not
affected by application of APV, however, the mean velocity of spread was
reduced from 0.20 m/s to 0.12 m/s. In conclusion, the large size of calcium
transients and of their NMDA receptor dependent components in stratum
pyramidale or stratum oriens as well as shortest onset latencies of calcium
transients at these sites suggest an important role of cell somata, basal
dendrites and possibly of local circuit excitatory interactions for the
generation and spread of epileptiform activity.
Received 16 January 1996; accepted in final form 28 August 1996.
APS Manuscript Number J21-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996