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PMID: 10430953 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 16 ·1999-08-03 ·Pages 9391-6

Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB

Abstract

Rhythmic activity of neurons and heart cells is endowed by pacemaker channels that are activated by hyperpolarization and directly regulated by cyclic nucleotides (termed HCN channels). These channels constitute a multigene family, and it is assumed that the properties of each member are adjusted to fit its particular function in the cell in which it resides. Here we report the molecular and functional characterization of a human subtype hHCN4. hHCN4 transcripts are expressed in heart, brain, and testis. Within the brain, the thalamus is the predominant area of hHCN4 expression. Heterologous expression of hHCN4 produces channels of unusually slow kinetics of activation and inactivation. The mean potential of half-maximal activation (V(1/2)) was -75.2 mV. cAMP shifted V(1/2) by 11 mV to more positive values. The hHCN4 gene was mapped to chromosome band 15q24-q25. The characteristic expression pattern and the sluggish gating suggest that hHCN4 controls the rhythmic activity in both thalamocortical neurons and pacemaker cells of the heart.

MeSH Terms
Amino Acid Sequence Animals Chromosome Mapping Chromosomes, Human, Pair 15 Cyclic Nucleotide-Gated Cation Channels Humans Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channels/chemistry,genetics,physiology Kinetics Male Membrane Potentials Mice Molecular Sequence Data Muscle Proteins Myocardium/metabolism Organ Specificity Potassium Channels Sequence Alignment Sequence Homology, Amino Acid Testis/metabolism Thalamus/metabolism Transcription, Genetic
Chemicals
Cyclic Nucleotide-Gated Cation Channels HCN4 protein, human Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channels Muscle Proteins Potassium Channels
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Seifert R
Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, 52425 Jülich, Germany. r.seifert@fz-juelich.de
Scholten A
Gauss R
Mincheva A
Lichter P
Kaupp U B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.16.9391
Email
r.seifert@fz-juelich.de
Published
1999-08-03
Pages
9391-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17793
Subset
IM
Databases
GENBANK
AJ238850
External Links
PubMed source DOI: 10.1073/pnas.96.16.9391 PMC Full Text View journal details
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