Molecular and functional analysis of hyperpolarization-activated pacemaker channels in the hippocampus after entorhinal cortex lesion

A. U. Bräuer, N. E. Savaskan, M. H P Kole, M. Plaschke, Lisa M Monteggia, E. J. Nestler, E. Simbürger, R. A. Deisz, O. Ninnemann, R. Nitsch

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Abstract

Differential display of hippocampal tissue after entorhinal cortex lesion (ECL) revealed decreases in mRNA encoding the neuronal hyperpolarization-activated, cyclic nucleotide-gated channel HCN1. In situ hybridization confirmed that hippocampal transcripts of HCN1, but not HCN2/3/4, are down-regulated after ECL. Expression recovered at ∼21 days after lesion (dal). Immunohistochemistry demonstrated a corresponding regulation of HCN1 protein expression in CA1-CA3 dendrites, hilar mossy cells and interneurons, and granule cells. Patch-clamp recordings in the early phase after lesion from mossy cells and hilar interneurons revealed an increase in the fast time constant of current activation and a profound negative shift in voltage activation of Ih. Whereas current activation recovered at 30 dal, the voltage activation remained hyperpolarized in mossy cells and hilar interneurons. Granule cells, however, were devoid of any detectable somatic Ih currents. Hence, denervation of the hippocampus decreases HCN1 and concomitantly the Ih activity in hilar neurons, and the recovery of h-current activation kinetics occurs parallel to postlesion sprouting.

Original languageEnglish (US)
Pages (from-to)2689-2701
Number of pages13
JournalFASEB Journal
Volume15
Issue number14
DOIs
StatePublished - Dec 22 2001

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Keywords

  • DDRT-PCR/ECL
  • HCN
  • Hippocampus
  • I

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Bräuer, A. U., Savaskan, N. E., Kole, M. H. P., Plaschke, M., Monteggia, L. M., Nestler, E. J., Simbürger, E., Deisz, R. A., Ninnemann, O., & Nitsch, R. (2001). Molecular and functional analysis of hyperpolarization-activated pacemaker channels in the hippocampus after entorhinal cortex lesion. FASEB Journal, 15(14), 2689-2701. https://doi.org/10.1096/fj.01-0235com