TY  - JOUR
AU  - Kanyshkova, T.
AU  - Pawlowski, M.
AU  - Meuth, P.
AU  - Dube, C.
AU  - Bender, R. A.
AU  - Brewster, A. L..
AU  - Baumann, A.
AU  - Baram, T. Z.
AU  - Pape, H.-C.
AU  - Budde, T.
TI  - Postnatal expression pattern of HCN channel isoforms in thalamic neurons: Relationship to maturation of thalamocortical oscillations
JO  - The journal of neuroscience
VL  - 29
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.
M1  - PreJuSER-5103
SP  - 8857 - 8847
PY  - 2009
N1  - 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.
AB  - 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.
KW  - Animals
KW  - Animals, Newborn
KW  - Biological Clocks: physiology
KW  - Cerebral Cortex: growth & development
KW  - Cerebral Cortex: metabolism
KW  - Cyclic Nucleotide-Gated Cation Channels: biosynthesis
KW  - Cyclic Nucleotide-Gated Cation Channels: genetics
KW  - Gene Expression Regulation, Developmental: physiology
KW  - Ion Channels: biosynthesis
KW  - Ion Channels: genetics
KW  - Neural Pathways: growth & development
KW  - Neural Pathways: metabolism
KW  - Neurons: metabolism
KW  - Neurons: physiology
KW  - Potassium Channels: biosynthesis
KW  - Potassium Channels: genetics
KW  - Protein Isoforms: biosynthesis
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Thalamus: growth & development
KW  - Thalamus: metabolism
KW  - Cyclic Nucleotide-Gated Cation Channels (NLM Chemicals)
KW  - HCN2 potassium channel (NLM Chemicals)
KW  - HCN3 protein, rat (NLM Chemicals)
KW  - HCN4 protein, rat (NLM Chemicals)
KW  - Ion Channels (NLM Chemicals)
KW  - Potassium Channels (NLM Chemicals)
KW  - Protein Isoforms (NLM Chemicals)
KW  - hyperpolarization-activated cation channel (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19587292
C2  - pmc:PMC2768285
UR  - <Go to ISI:>//WOS:000267818400026
DO  - DOI:10.1523/JNEUROSCI.0689-09.2009
UR  - https://juser.fz-juelich.de/record/5103
ER  -