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Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites

Nature Neuroscience volume 5, pages 1185–1193 (2002)Cite this article

Abstract

An ion channel's function depends largely on its location and density on neurons. Here we used high-resolution immunolocalization to determine the subcellular distribution of the hyperpolarization-activated and cyclic-nucleotide-gated channel subunit 1 (HCN1) in rat brain. Light microscopy revealed graded HCN1 immunoreactivity in apical dendrites of hippocampal, subicular and neocortical layer-5 pyramidal cells. Quantitative comparison of immunogold densities showed a 60-fold increase from somatic to distal apical dendritic membranes. Distal dendritic shafts had 16 times more HCN1 labeling than proximal dendrites of similar diameters. At the same distance from the soma, the density of HCN1 was significantly higher in dendritic shafts than in spines. Our results reveal the complex cell surface distribution of voltage-gated ion-channels, and predict its role in increasing the computational power of single neurons via subcellular domain and input-specific mechanisms.

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Figure 1: Immunoblot analysis of rat brain with HCN1 antibodies.
Figure 2: Light microscopic demonstration of HCN1 immunoreactivity in rat neocortex.
Figure 3: Double-immunofluorescence labeling of HCN1 with the rabbit (left) and guinea pig (right) antibodies in hippocampus (a, b) and somatosensory cortex (c, d).
Figure 4: Electron-microscopic immunogold localization of HCN1 immunoreactivity.
Figure 5: Electron micrographs showing the subcellular distribution of HCN1 immunoreactivity in the subiculum.
Figure 6: Quantitative evaluation of immunogold distribution of HCN1 in subicular pyramidal cells.

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Acknowledgements

Z.N. received grants from the Hungarian Science Foundation (T032309), the Howard Hughes Medical Institute, the James S. McDonnell Foundation, the Wellcome Trust and the Boehringer Ingelheim Fund. Z.N. and R.S. received grants from CREST—Japan Science and Technology Corporation. G.T. is funded by the Wellcome Trust.

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  1. Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony Street 43, Budapest, 1083, Hungary

    Andrea Lörincz & Zoltan Nusser

  2. Department of Comparative Physiology, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary

    Andrea Lörincz & Gábor Tamás

  3. Division of Cerebral Structure, National Institute for Physiological Sciences, The Graduate University for Advanced Studies, School of Life Science, Okazaki, CREST Japan Science and Technology Corporation, Kawaguchi, 444-8585, Okazaki, Japan

    Takuya Notomi & Ryuichi Shigemoto

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Lörincz, A., Notomi, T., Tamás, G. et al. Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites. Nat Neurosci 5, 1185–1193 (2002). https://doi.org/10.1038/nn962

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