Article abstract


Nature Neuroscience 12, 577 - 584 (2009)
Published online: 12 April 2009 | doi:10.1038/nn.2307

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

Meena S George1, L F Abbott1,2 & Steven A Siegelbaum1,3,4


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 (Ih) 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 Ih was caused by its interaction with the delayed-rectifier M-type K+ current. In this manner, Ih can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.

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  1. Department of Neuroscience, Columbia University, New York, New York, USA.
  2. Departments of Physiology and Cellular Biophysics, Columbia University, New York, New York, USA.
  3. Department of Pharmacology, Columbia University, New York, New York, USA.
  4. Howard Hughes Medical Institute, Columbia University, New York, New York, USA.

Correspondence to: Steven A Siegelbaum1,3,4 e-mail: sas8@columbia.edu



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