Electrophysiological studies have shown that decreases in extracellular Ca2+ concentration and increases in extracellular K+ concentration cause non-synaptic seizure-like neuronal activity in the hippocampus. Using the calcium imaging technique, we investigated the role of intracellular Ca2+ concentration in the cause of non-synaptic seizure-like neuronal activity. Rat hippocampal slice culture was loaded with calcium indicator dye. Non-synaptic seizure-like neuronal activity was induced by low Ca2+/high K+ solution. The calcium imaging, with a confocal laser scanning microscope and extracellular field recording were made simultaneously. Pharmacological inhibitors were used to examine the mechanism of the intracellular Ca2+ changes. As a result, intracellular Ca2+ oscillation occurred in neurons in a nonuniform fashion after replacing the solution, and then, gradual massive synchronization occurred in the large population. This massive synchronized Ca2+ oscillation propagated transversely through the CA1 area at a velocity of 4.2–6.8 mm/min. A negative shift, which reflects seizure-like neuronal activity, was observed in extracellular field recording, corresponding to the synchronized intracellular Ca2+ oscillation. Voltage-dependent calcium channel blocker and gap junction blocker inhibited this synchronization and the propagation. In conclusion, using the calcium-imaging technique, we demonstrated dynamic changes in synchronization and propagation of intracellular Ca2+ oscillation, which corresponded to non-synaptic epileptiform activity. The role of gap junction as a contributing mechanism was speculated.
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