Cited by 203Ion channel regulation and functionNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex

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Kalmbach, Brian E., Buchin, Anatoly, Long, Brian, Close, Jennie, Nandi, Anirban, Miller, Jeremy A., Bakken, Trygve E., Hodge, Rebecca D. +15 more·2018·Neuron

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Abstract

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provide evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.

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Crossref · 10.1016/j.neuron.2018.10.012

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Authors
Kalmbach, B. E., Buchin, A., Long, B., Close, J., Nandi, A., Miller, J. A., Bakken, T. E., Hodge, R. D., Chong, P., de Frates, R., Dai, K., Maltzer, Z., Nicovich, P. R., Keene, C. D., Silbergeld, D. L., Gwinn, R. P., Cobbs, C., Ko, A. L., Ojemann, J. G., Koch, C., Anastassiou, C. A., Lein, E. S., & Ting, J. T.
Affiliations
  • Allen Institute for Brain Science (US)
  • University of Washington (US)
  • Swedish Medical Center (US)
Corresponding author
  • Kalmbach, Brian E.
  • Ting, Jonathan T.
Venue
Neuron
Publisher
Elsevier BV
Published
2018-12
Volume
100
Issue
5
Pages
1194-1208.e5
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2899419202
Cited by
203
References
84
Citations by year
2026: 12 · 2025: 30 · 2024: 31 · 2023: 45 · 2022: 28 · 2021: 27 · 2020: 21 · 2019: 9
FWCI
5.07
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (U01MH114812)
  • Chan Zuckerberg Initiative (2017-174399)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
hyperpolarization-activated cation channels, HCN1, cerebral cortex, cortical depth, membrane properties, theta oscillations, excitatory neurons, single-cell RNA sequencing
MeSH terms
Adult, Animals, Cell Membrane, Cerebral Cortex, Female, Humans, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Species Specificity, Potassium Channels, Pyramidal Cells, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels

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