HCN hyperpolarization-activated cation channels inhibit EPSPs by interactions with M-type K(+) channels
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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.
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Distal EPSPs in CA1 neurons are locally attenuated by active properties of dendrites, including high density of HCN1 channels in distal dendrites.
“Second, distal EPSPs in CA1 neurons are locally attenuated by the active properties of the dendrites, including the presence of a very high density of HCN1 channels in the distal dendrites, which act as a depolarizing shunt conductance (George et al., 2009; Magee, 1999).”
From Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop (2010) · cites this paper as George et al., 2009
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- Authors
- George, M. S., Abbott, L. F., & Siegelbaum, S. A.
- Affiliations
- Columbia University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Siegelbaum, Steven A
- Venue
- Nature Neuroscience
- Published
- 2009-04-12
- Volume
- 12
- Issue
- 5
- Pages
- 577-584
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2674138
- OpenAlex
- W1978116811
- Cited by
- 187
- References
- 52
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 9 · 2022: 14 · 2021: 12 · 2020: 17 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 10 · 2014: 10 · 2013: 14 · 2012: 22
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5-DP1-OD114-02, DP1OD000114)
- National Institute of Mental Health (R01MH080745, MH80745)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- HCN channels, hyperpolarization-activated current, M-type potassium current, excitatory postsynaptic potentials, dendritic processing, synaptic integration, CA1 hippocampal neurons, voltage-gated ion channels, synaptic efficacy
- MeSH terms
- Action Potentials, Animals, Computer Simulation, Hippocampus, Synaptic Transmission, Organ Culture Techniques, Potassium Channels, Pyramidal Cells, Excitatory Postsynaptic Potentials, Mice, KCNQ1 Potassium Channel, Cyclic Nucleotide-Gated Cation Channels, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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