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Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate
X Zhang1, A A Velumian, O T Jones
1Toronto Hospital Research Institute, Department of Physiology, University of Toronto, Ontario, Canada.
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 microM.
Results:
TPM inhibited L-type currents and was more effective at 10 microM than at 50 microM, 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 microM).
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.