Voltage-dependent calcium channel abnormalities in hippocampal CA3 neurons of spontaneously epileptic rats

Abstract

Purpose: Hippocampal CA3 neurons of spontaneously epileptic rats (SER; zi/zi, tm/tm), which show both absence-like seizures and tonic convulsions, exhibit a long-lasting depolarization shift with repetitive firing with a single stimulation of mossy fibers. Therefore a whole-cell patch-clamp study using temporarily dissociated hippocampal CA3 neurons from SER was performed to elucidate whether such abnormal excitability was due to abnormalities in voltage-dependent Ca2+ channels (VDCCs). Methods: Hippocampal CA3 neurons were temporarily dissociated with enzymatic and mechanical treatments. In a voltage-clamp mode with whole-cell recording, depolarizing step pulses were applied to induce Ca2+ currents in the presence of tetrodotoxin and tetraethylammonium. Results: The threshold level of the Ca2+ current induced by depolarizing pulses was found to be lower in hippocampal CA3 neurons of SER compared with those of control Wistar rats. In addition, the Ca 2+ current peak amplitude was greater, and decay of the current was weaker in CA3 neurons of SER than in those of normal Wistar rats. Conclusions: These findings suggest that enhancements of Ca2+ influx into hippocampal CA3 neurons due to the easier activation properties of VDCCs, as well as a decrease in decay, are involved in SER epileptic seizures. © 2007 International League Against Epilepsy.