Journal Article

PreJuSER-5103

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Postnatal expression pattern of HCN channel isoforms in thalamic neurons: Relationship to maturation of thalamocortical oscillations

Kanyshkova, T. ; Pawlowski, M. ; Meuth, P. ; Dube, C. ; Bender, R. A. ; Brewster, A. L. ; Baumann, A.FZJ* ; Baram, T. Z. ; Pape, H.-C. ; Budde, T.

2009
Soc. Washington, DC

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Please use a persistent id in citations: doi:10.1523/JNEUROSCI.0689-09.2009

Abstract: Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are the molecular substrate of the hyperpolarization-activated inward current (I(h)). Because the developmental profile of HCN channels in the thalamus is not well understood, we combined electrophysiological, molecular, immunohistochemical, EEG recordings in vivo, and computer modeling techniques to examine HCN gene expression and I(h) properties in rat thalamocortical relay (TC) neurons in the dorsal part of the lateral geniculate nucleus and the functional consequence of this maturation. Recordings of TC neurons revealed an approximate sixfold increase in I(h) density between postnatal day 3 (P3) and P106, which was accompanied by significantly altered current kinetics, cAMP sensitivity, and steady-state activation properties. Quantification on tissue levels revealed a significant developmental decrease in cAMP. Consequently the block of basal adenylyl cyclase activity was accompanied by a hyperpolarizing shift of the I(h) activation curve in young but not adult rats. Quantitative analyses of HCN channel isoforms revealed a steady increase of mRNA and protein expression levels of HCN1, HCN2, and HCN4 with reduced relative abundance of HCN4. Computer modeling in a simplified thalamic network indicated that the occurrence of rhythmic delta activity, which was present in the EEG at P12, differentially depended on I(h) conductance and modulation by cAMP at different developmental states. These data indicate that the developmental increase in I(h) density results from increased expression of three HCN channel isoforms and that isoform composition and intracellular cAMP levels interact in determining I(h) properties to enable progressive maturation of rhythmic slow-wave sleep activity patterns.

Keyword(s): Animals (MeSH) ; Animals, Newborn (MeSH) ; Biological Clocks: physiology (MeSH) ; Cerebral Cortex: growth & development (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Cyclic Nucleotide-Gated Cation Channels: biosynthesis (MeSH) ; Cyclic Nucleotide-Gated Cation Channels: genetics (MeSH) ; Gene Expression Regulation, Developmental: physiology (MeSH) ; Ion Channels: biosynthesis (MeSH) ; Ion Channels: genetics (MeSH) ; Neural Pathways: growth & development (MeSH) ; Neural Pathways: metabolism (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: physiology (MeSH) ; Potassium Channels: biosynthesis (MeSH) ; Potassium Channels: genetics (MeSH) ; Protein Isoforms: biosynthesis (MeSH) ; Rats (MeSH) ; Rats, Sprague-Dawley (MeSH) ; Thalamus: growth & development (MeSH) ; Thalamus: metabolism (MeSH) ; Cyclic Nucleotide-Gated Cation Channels ; HCN2 potassium channel ; HCN3 protein, rat ; HCN4 protein, rat ; Ion Channels ; Potassium Channels ; Protein Isoforms ; hyperpolarization-activated cation channel ; J

Note: This work was supported by Deutsche Forschungsgemeinschaft Grants BU 1019/8-1 and BE 4107/2-1, Interdisziplinares Zentrum fur Klinische Forschung Grant Bud/005/07, and National Institutes of Health Grants NS 35439 and NS 45540. This work was done in partial fulfillment of the MD thesis of M. P. and the PhD thesis of P. M. We thank A. Markovic, E. Nass, and S. Ruppel for excellent technical assistance.

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Contributing Institute(s):

1. Zelluläre Biophysik (ISB-1)

Research Program(s):

1. Programm Biosoft (N03)

Appears in the scientific report 2009

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