Synergistic inhibitory action of oxcarbazepine on INa and IK (Huang et al. 2008)


"Oxcarbazepine (OXC), one of the newer anti-epileptic drugs, has been demonstrating its efficacy on wide-spectrum neuropsychiatric disorders. ... With the aid of patch-clamp technology, we first investigated the effects of OXC on ion currents in NG108-15 neuronal cells differentiated with cyclic AMP. We found OXC ... caused a reversible reduction in the amplitude of voltage-gated Na+ current (INa) ... and produce(d) a significant prolongation in the recovery of INa inactivation. ... Moreover, OXC could suppress the amplitude of delayed rectifier K+ current (IK(DR)), with no effect on M-type K+ current (IK(M)). ... Furthermore, the simulations, based on hippocampal pyramidal neurons (Pinsky-Rinzel model) and a network of the Hodgkin-Huxley model, were analysed to investigate the effect of OXC on action potentials. Taken together, our results suggest that the synergistic blocking effects on INa and IK(DR) may contribute to the underlying mechanisms through which OXC affects neuronal function in vivo."

Model Type: Neuron or other electrically excitable cell; Channel/Receptor

Cell Type(s): NG108-15 neuronal cell

Currents: I K; I Sodium

Model Concept(s): Ion Channel Kinetics; Simplified Models; Action Potentials

Simulation Environment: XPPAUT

Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]

References:

Huang CW, Huang CC, Lin MW, Tsai JJ, Wu SN. (2008). The synergistic inhibitory actions of oxcarbazepine on voltage-gated sodium and potassium currents in differentiated NG108-15 neuronal cells and model neurons. The international journal of neuropsychopharmacology. 11 [PubMed]


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