Modulation of High‐Voltage–Activated Calcium Channels in Dentate Granule Cells by Topiramate

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Abstract
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 Ca2+ 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 Ca2+ currents may be an important anticonvulsant mechanism of TPM.