Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with established antiepileptic efficacy in generalized epilepsy and partial epilepsy. However, its effects on ion currents and membrane potential remain largely unclear. In this study, we investigated the effect of LEV on differentiated NG108-15 neurons. ... Simulation studies in a modified Hodgkin-Huxley neuron and network unraveled that the reduction of slowly inactivating IK(DR) resulted in membrane depolarization accompanied by termination of the firing of action potentials in a stochastic manner. Therefore, the inhibitory effects on slowly inactivating IK(DR) (Kv3.1-encoded current) may constitute one of the underlying mechanisms through which LEV affects neuronal activity in vivo.
Genes: Kv3.1 KCNC1
Simulation Environment: XPPAUT
Huang CW, Tsai JJ, Huang CC, Wu SN. (2009). Experimental and simulation studies on the mechanisms of levetiracetam-mediated inhibition of delayed-rectifier potassium current (KV3.1): contribution to the firing of action potentials. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 60 [PubMed]