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Journal of Neuroscience, Vol 14, 4308-4317, Copyright © 1994 by Society for Neuroscience
Modulation of gap junctional mechanisms during calcium-free induced field burst activity: a possible role for electrotonic coupling in epileptogenesis
JL Perez-Velazquez, TA Valiante and PL Carlen
Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
To date, there is little experimental evidence supporting or refuting
electrotonic interactions through gap junctions in the generation and/or
spread of seizure activity in the mammalian brain. We have studied gap
junctional mechanisms in the in vitro calcium-free induced model of
epilepsy using electrophysiological and staining techniques in the CA1 area
of the hippocampus. Lucifer yellow staining of CA1 pyramidal neurons
revealed that dye coupling was increased 2.3 times in hippocampal slices
made hyperexcitable by perfusion with calcium-free artificial cerebrospinal
fluid (aCSF). Furthermore, multiple neuronal dye coupling (triplets,
quintuplets) was observed in these conditions but never in control
(standard aCSF). Under conditions that reduce gap junctional conductance
(intracellular acidification, octanol, halothane), seizure-like activity
was suppressed in the CA1 area in this epilepsy model, whereas increasing
gap junctional conductance by intracellular alkalinization increased the
frequency and duration of field burst events. Intracellular acidification
also reduced dye coupling as well as the frequency of fast prepotentials
(electrotonic potentials) without altering neuronal firing frequency.
Simultaneous extracellular field and single whole-cell recordings revealed
suppression of synchronization between neuronal firing and spontaneous
field burst activity during acidification. These observations indicate an
apparent increase in electrotonic coupling during calcium-free induced
spontaneous rhythmic field burst activity in the CA1 area of the
hippocampus and that electrotonic coupling may contribute substantially to
the synchronization of neuronal firing underlying seizure-like events.
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