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 Ca2+ currents into different subtypes. Three concentrations of TPM were tested: 1, 10, and 50 mu M. Results: TPM inhibited L-type currents and was more effective at 10 mu M th an at 50 mu M, suggesting that there may be an optimal concentration at whi ch TPM decreases L-type currents. Non-L-type currents were transiently incr eased by TPM at a high concentration (50 mu M). Conclusions: Because the location of L-type calcium channels on soma and pr oximal dendrites gives these channels a crucial role in controlling dendrit ic excitability and in providing calcium for intracellular effectors, the d ecrease in the L-type HVA Ca2+ currents may be an important anticonvulsant mechanism of TPM.