The Effects of Levetiracetam on Glutamatergic Synaptic Transmission

Department of Biology, University of Kentucky, Lexington, KY, USA, 40506-0225

Epilepsy is a neurological disorder characterized by recurring, unpredictable seizures. Its disease burden is high, ranking fourth in the world’s neurological disorders behind tension-type headaches, migraines, and Alzheimer’s disease. The commonly used antiepileptic drug levetiracetam (Keppra) reduces epileptic seizures; however, the exact mechanism is not known. Some studies suggest that sodium and/or potassium ionic channels are directly altered, reducing membrane excitability. Yet others suggest it interacts with synaptic vesicle protein SV2 to alter synaptotagmin's (a calcium sensor vesicle protein) action in the presynaptic nerve terminal to reduce excitability. The aim in this study was to examine whether synaptic transmission would be reduced in a model glutamatergic synaptic preparation. In this study, the glutamatergic synapses at crayfish neuromuscular junctions (NMJs) were used to assess the drug's action. The evoked excitatory junction potentials of the crayfish NMJ were unexpectedly enhanced within 20 min of stimulation with pulse trains following static incubation of 10 min exposure to 1 mM doses. Repetitive stimulation for 2 min and incubation for 10 min without stimulation did not show an effect. This project was an authentic course-based undergraduate research experience (ACURE) in a neurophysiology teaching laboratory with 16 students. It appears levetiracetam acts differently in different animal models and varied experimental conditions are required to note the effects.

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