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Gabapentin Increases the Hyperpolarization‐activated Cation Current I h in Rat CA1 Pyramidal Cells
Author(s) -
Surges Rainer,
Freiman Thomas M.,
Feuerstein Thomas J.
Publication year - 2003
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2003.36802.x
Subject(s) - anticonvulsant , hyperpolarization (physics) , chemistry , hippocampal formation , epilepsy , biophysics , gabapentin , membrane potential , intracellular , neuroscience , hippocampus , pharmacology , medicine , psychology , stereochemistry , biology , biochemistry , alternative medicine , pathology , nuclear magnetic resonance spectroscopy
Summary: Purpose: Gabapentin (GBP) is a commonly used drug in the treatment of partial seizures, but its mode of action is still unclear. The genesis of seizures in temporal lobe epilepsy is thought to be crucially influenced by intrinsic membrane properties. Because the I h substantially contributes to the intrinsic membrane properties of neurons, the effects of GBP on the I h were investigated in CA1 pyramidal cells of rat hippocampus. Methods: CA1 pyramidal cells in hippocampal slices were examined by using the whole‐cell patch‐clamp technique. Results: GBP increased the I h amplitude in a concentration‐dependent manner mainly by increasing the conductance, without significant changes in the activation properties or in the time course of I h . The effects ranged from ∼20% at 50 μ M , ∼25% at 75 μ M , to ∼35% at 100 μ M GBP (at –110 mV). In the presence of intracellular cyclic adenosine monophosphate (cAMP), the effects of GBP on I h were similar to those obtained in the absence of cAMP. Conclusions: These results suggest that GBP increases the I h through a cAMP‐independent mechanism. Because the applied GBP concentrations were in a clinically relevant range, the observed effect may contribute to the anticonvulsant action of GBP in partial seizures and may represent a new concept of how this anticonvulsant drug works.