Glutamate Uptake Inhibition Enhances Epileptiform Activity in Rat Neocortex
Abstract number :
A.05
Submission category :
Year :
2001
Submission ID :
2118
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
S. Campbell; J.J. Hablitz, PhD, Dept. of Neurobiology, Univ. of Alabama at Birmingham, Birmingham, AL
RATIONALE: The role of glutamate uptake in determining the duration of excitatory postsynaptic currents (EPSCs) varies between synapses. Epileptiform activity results from synchronized neuronal discharges which likely release large amounts of glutamate, yet the role of transporters during such responses is unclear. We therefore examined the effect of uptake inhibition on epileptiform activity in rat neocortex.
METHODS: Slices of neocortex were prepared from rats 15-23 days of age. Whole cell patch clamp recordings were obtained from pyramidal cells in layer II/III of prefrontal cortex. Epileptiform activity was induced by stimulation in layer IV in the presence of bath applied bicuculline. The glutamate transporter blockers D, L-threo-b-hydroxyaspartic acid (THA) and dihydrokainic acid (DHK) were bath applied at 100 uM.
RESULTS: In the presence of bicuculline, weak stimulation evoked EPSCs whereas stronger stimulation elicited epileptiform discharges. EPSCs evoked by weak stimulation were not significantly affected by THA or DHK. When epileptiform discharges were evoked, transport blockers increased the amplitude and/or area of the response. The peak amplitude of epileptiform events increased with the addition of THA and DHK (626 vs 803 pA). Increasing the temperature from 24-25 to 30[degree]C resulted in a general increase in the mean peak amplitude (1494 pA). At the higher temperature, THA addition caused further enhancement of the response (2164 pA). These effects were reversible upon washing.
CONCLUSIONS: Our results suggest that glutamate transporters may be important in curtailing epileptiform activity. Increases in epileptiform activity in the presence of transport blockers presumably results from increases in glutamate levels and enhanced neuronal excitability. These results suggest that glutamate transporters serve to regulate the amplitude and duration of epileptiform discharges. Changes in transporter expression and/or dysfunctional glutamate reuptake may contribute to hyperexcitability in epileptic neocortex.
Support: NS18145 and NS22373