Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy

Abstract

Influx of calcium ion (Ca ++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca ++ indicator, changes in cytosolic free calcium ([Ca ++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca ++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca ++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (ICBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca ++]i signal ratio started to increase 19 ± 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca ++]i is presumably due to a synaptic Ca ++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and lCBF increased by 17 ± 8% and 68 ± 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis.