Gabapentin promotes inhibition by enhancing hyperpolarization-activated cation currents and spontaneous firing in hippocampal CA1 interneurons

Abstract

The H-current ( I H) regulates membrane electrical activity in many excitable cells. The antiepileptic drug gabapentin (GBP) has been shown to increase I H in hippocampal area CA1 pyramidal neurons, and this has been proposed as an anticonvulsant mechanism of action. I H also regulates excitability in some types of hippocampal interneuron that provide synaptic inhibition to CA1 pyramidal neurons, suggesting that global pharmacological I H enhancement could have more complex effects on the local synaptic network. However, whether I H in CA1 interneurons is modulated by GBP has not been examined. In this study, we tested the effects of GBP on I H on hippocampal area CA1 stratum oriens non-pyramidal neurons, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in immature rat brain slices. GBP (100 μM) increased I H in approximately 67% of interneurons that exhibited I H, with no apparent effect on cell types that did not exhibit I H. GBP also increased the frequency of spontaneous (but not miniature) inhibitory postsynaptic currents in pyramidal neurons without altering amplitudes or rise and decay times. These data indicate that I H in a subset of CA1 interneuron types can be increased by GBP, similarly to its effect on I H in pyramidal neurons, and further, that indirectly increased spontaneous inhibition of pyramidal neurons could contribute to its anticonvulsant effects.