X Zhang1, A A Velumian, O T Jones, P L Carlen. 1. Toronto Hospital Research Institute, Department of Physiology, University of Toronto, Ontario, Canada.
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 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.
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.
Authors: Sandra Ghelardoni; Richard P Bazinet; Stanley I Rapoport; Francesca Bosetti Journal: Psychopharmacology (Berl) Date: 2005-02-18 Impact factor: 4.530
Authors: G Curia; P Aracri; E Colombo; P Scalmani; M Mantegazza; G Avanzini; S Franceschetti Journal: Br J Pharmacol Date: 2007-02-05 Impact factor: 8.739