MODULATION OF GAP JUNCTIONAL MECHANISMS DURING CALCIUM-FREE INDUCED FIELD BURST ACTIVITY - A POSSIBLE ROLE FOR ELECTROTONIC COUPLING IN EPILEPTOGENESIS

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 o f epilepsy using electrophysiological and staining techniques in the C A 1 area of the hippocampus. Lucifer yellow staining of CA 1 pyramidal neurons revealed that dye coupling was increased 2.3 times in hippoca mpal slices made hyperexcitable by perfusion with calcium-free artific ial cerebrospinal fluid (aCSF). Furthermore, multiple neuronal dye cou pling (triplets, quintuplets) was observed in these conditions but nev er in control (standard aCSF). Under conditions that reduce gap juncti onal conductance (intracellular acidification, octanol, halothane), se izure-like activity was suppressed in the CA 1 area in this epilepsy m odel, whereas increasing gap junctional conductance by intracellular a lkalinization increased the frequency and duration of field burst even ts. Intracellular acidification also reduced dye coupling as well as t he frequency of fast prepotentials (electrotonic potentials) without a ltering neuronal firing frequency. Simultaneous extracellular field an d single whole-cell recordings revealed suppression of synchronization between neuronal firing and spontaneous field burst activity during a cidification. These observations indicate an apparent increase in elec trotonic coupling during calcium-free induced spontaneous rhythmic fie ld burst activity in the CA 1 area of the hippocampus and that electro tonic coupling may contribute substantially to the synchronization of neuronal firing underlying seizure-like events.