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

• Published in: Neuroscience letters 2011-04, Vol.494 (1), p.19-23
• Main Authors: Peng, Bi-Wen, Justice, Jason A., Zhang, Kun, Li, Jun-xu, He, Xiao-hua, Sanchez, Russell M.
• Format: Article
• Language: English
• Subjects: Amines - pharmacology; Analysis of Variance; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiology; Cyclohexanecarboxylic Acids - pharmacology; Electrophysiology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Gabapentin; gamma-Aminobutyric Acid - pharmacology; H-current; Hippocampus; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - physiology; Interneuron; Interneurons - drug effects; Interneurons - physiology; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neuropharmacology; Pharmacology. Drug treatments; Rats; Rats, Long-Evans; Slice; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.02.045

► Gabapentin increased I h in hippocampal interneurons. ► Gabapentin increased action potential firing in hippocampal pyramidal neurons. ► Gabapentin increased spontaneous inhibitory synaptic events in pyramidal neurons. ► Increasing in inhibition of principal neurons might be antiepileptic mechanism. 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.