Gabapentin increases the hyperpolarization-activated cation current Ih in rat CA1 pyramidal cells

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 lh 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 muM, similar to25% at 75 muM, to similar to35% at 100 muM 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.