Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate.
In this study, we assessed the effects of topiramate (TPM) on high-voltage-activated calcium channel (HVACC) currents in vitro.



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.



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).



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.
Zhang
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X
Toronto Hospital Research Institute, Department of Physiology, University of Toronto, Ontario, Canada.
Velumian
A A
AA
Jones
O T
OT
Carlen
P L
PL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D000077236:Topiramate
D000927:Anticonvulsants; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D000077236:Topiramate; D005632:Fructose