Abstract | PURPOSE: METHODS: Acutely isolated human hippocampal granule cells were examined by using the whole-cell configuration of the patch-clamp technique. RESULTS: PHT and CBZ produced a reversible, concentration-dependent inhibition of high-voltage-activated (HVA) Ca2+ currents without affecting voltage-dependent activation. The concentration-response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with half-maximal inhibition being obtained at 89 and 244 microM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole-brain concentration of 80 microM. In contrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady-state inactivation. PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/- 0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances. CONCLUSIONS: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.
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Authors | T B Schumacher, H Beck, C Steinhäuser, J Schramm, C E Elger |
Journal | Epilepsia
(Epilepsia)
Vol. 39
Issue 4
Pg. 355-63
(Apr 1998)
ISSN: 0013-9580 [Print] United States |
PMID | 9578025
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetates
- Amines
- Anticonvulsants
- Calcium Channels
- Cyclohexanecarboxylic Acids
- Carbamazepine
- gamma-Aminobutyric Acid
- Phenytoin
- Gabapentin
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Topics |
- Acetates
(pharmacology, therapeutic use)
- Adult
- Amines
- Anticonvulsants
(pharmacology, therapeutic use)
- Calcium Channels
(drug effects)
- Carbamazepine
(pharmacology, therapeutic use)
- Cyclohexanecarboxylic Acids
- Dentate Gyrus
(cytology)
- Epilepsy, Temporal Lobe
(drug therapy, pathology, physiopathology)
- Gabapentin
- Hippocampus
(cytology, drug effects, pathology)
- Humans
- Membrane Potentials
(drug effects, physiology)
- Neurons
(drug effects, physiology)
- Patch-Clamp Techniques
- Phenytoin
(pharmacology, therapeutic use)
- Pyramidal Cells
(drug effects, physiology)
- gamma-Aminobutyric Acid
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