Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS.

Details

Serval ID
serval:BIB_4440D3A5739D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS.
Journal
Journal of Neuroscience
Author(s)
Santoro B., Chen S., Luthi A., Pavlidis P., Shumyatsky G.P., Tibbs G.R., Siegelbaum S.A.
ISSN
0270-6474
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
20
Number
14
Pages
5264-5275
Language
english
Abstract
The hyperpolarization-activated cation current (termed I(h), I(q), or I(f)) was recently shown to be encoded by a new family of genes, named HCN for hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective. When expressed in heterologous cells, each HCN isoform generates channels with distinct activation kinetics, mirroring the range of biophysical properties of native I(h) currents recorded in different classes of neurons. To determine whether the functional diversity of I(h) currents is attributable to different patterns of HCN gene expression, we determined the mRNA distribution across different regions of the mouse CNS of the three mouse HCN genes that are prominently expressed there (mHCN1, 2 and 4). We observe distinct patterns of distribution for each of the three genes. Whereas mHCN2 shows a widespread expression throughout the CNS, the expression of mHCN1 and mHCN4 is more limited, and generally complementary. mHCN1 is primarily expressed within neurons of the neocortex, hippocampus, and cerebellar cortex, but also in selected nuclei of the brainstem. mHCN4 is most highly expressed within neurons of the medial habenula, thalamus, and olfactory bulb, but also in distinct neuronal populations of the basal ganglia. Based on a comparison of mRNA expression with an electrophysiological characterization of native I(h) currents in hippocampal and thalamic neurons, our data support the idea that the functional heterogeneity of I(h) channels is attributable, in part, to differential isoform expression. Moreover, in some neurons, specific functional roles can be proposed for I(h) channels with defined subunit composition.
Keywords
Animals, Biological Clocks, Brain, Cells, Cultured, Central Nervous System, Cyclic Nucleotide-Gated Cation Channels, Gene Expression, Hippocampus, Ion Channels, Male, Mice, Mice, Inbred C57BL, Multigene Family, Muscle Proteins, Nerve Tissue Proteins, Neurons, Oocytes, Patch-Clamp Techniques, Potassium Channels, RNA, Messenger, Recombinant Proteins, Spinal Cord, Thalamus, Xenopus
Pubmed
Web of science
Create date
26/02/2009 14:45
Last modification date
20/08/2019 13:48
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