HCN hyperpolarization-activated cation channels inhibit EPSPs by interactions with M-type K(+) channels

Nat Neurosci. 2009 May;12(5):577-84. doi: 10.1038/nn.2307. Epub 2009 Apr 12.


The processing of synaptic potentials by neuronal dendrites depends on both their passive cable properties and active voltage-gated channels, which can generate complex effects as a result of their nonlinear properties. We characterized the actions of HCN (hyperpolarization-activated cyclic nucleotide-gated cation) channels on dendritic processing of subthreshold excitatory postsynaptic potentials (EPSPs) in mouse CA1 hippocampal neurons. The HCN channels generated an excitatory inward current (I(h)) that exerted a direct depolarizing effect on the peak voltage of weak EPSPs, but produced a paradoxical hyperpolarizing effect on the peak voltage of stronger, but still subthreshold, EPSPs. Using a combined modeling and experimental approach, we found that the inhibitory action of I(h) was caused by its interaction with the delayed-rectifier M-type K(+) current. In this manner, I(h) can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Computer Simulation
  • Cyclic Nucleotide-Gated Cation Channels / physiology*
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / physiology*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • KCNQ1 Potassium Channel / physiology
  • Mice
  • Organ Culture Techniques
  • Potassium Channels / physiology*
  • Pyramidal Cells / physiology*
  • Synaptic Transmission / physiology*


  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • KCNQ1 Potassium Channel
  • Kcnq1 protein, mouse
  • Potassium Channels