Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate

Purpose: In this study, we assessed the effects of topiramate (TPM) on high-voltage-activated calcium channel (HVACC) currents in vitro. Methods: HVACC currents were recorded from rat dentate gyrus granule cells by using whole-cell patch-clamp techniques. The biophysical properties of HVACCs were used to separate voltage-activated Ca 2+ currents into different subtypes. Three concentrations of TPM were tested: 1, 10, and 50 μM. Results: TPM inhibited L-type currents and was more effective at 10 μM than at 50 μM, suggesting that there may be an optimal concentration at which TPM decreases L-type currents. Non-L-type currents were transiently increased by TPM at a high concentration (50 μM). Conclusions: Because the location of L-type calcium channels on soma and proximal dendrites gives these channels a crucial role in controlling dendritic excitability and in providing calcium for intracellular effectors, the decrease in the L-type HVA Ca 2+ currents may be an important anticonvulsant mechanism of TPM.