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

Neurosci Lett. 2011 Apr 20;494(1):19-23. doi: 10.1016/j.neulet.2011.02.045. Epub 2011 Feb 23.


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 (100μM) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology*
  • Analysis of Variance
  • Animals
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / physiology
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Gabapentin
  • Inhibitory Postsynaptic Potentials / drug effects*
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / drug effects*
  • Interneurons / physiology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Rats
  • Rats, Long-Evans
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / pharmacology*


  • Amines
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • gamma-Aminobutyric Acid
  • Gabapentin