PMID- 10430953
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 16
DP  - 1999 Aug 3
TI  - Molecular characterization of a slowly gating human hyperpolarization-activated
      channel predominantly expressed in thalamus, heart, and testis.
PG  - 9391-6
AB  - 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.
FAU - Seifert, R
AU  - Seifert R
AD  - Institut fur Biologische Informationsverarbeitung, Forschungszentrum Julich,
      52425 Julich, Germany. r.seifert@fz-juelich.de
FAU - Scholten, A
AU  - Scholten A
FAU - Gauss, R
AU  - Gauss R
FAU - Mincheva, A
AU  - Mincheva A
FAU - Lichter, P
AU  - Lichter P
FAU - Kaupp, U B
AU  - Kaupp UB
LA  - eng
SI  - GENBANK/AJ238850
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cyclic Nucleotide-Gated Cation Channels)
RN  - 0 (HCN4 protein, human)
RN  - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels)
RN  - 0 (Ion Channels)
RN  - 0 (Muscle Proteins)
RN  - 0 (Potassium Channels)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 15
MH  - Cyclic Nucleotide-Gated Cation Channels
MH  - Humans
MH  - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
MH  - Ion Channels/chemistry/*genetics/*physiology
MH  - Kinetics
MH  - Male
MH  - Membrane Potentials
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Muscle Proteins
MH  - Myocardium/*metabolism
MH  - Organ Specificity
MH  - Potassium Channels
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Testis/*metabolism
MH  - Thalamus/*metabolism
MH  - Transcription, Genetic
PMC - PMC17793
EDAT- 1999/08/04 00:00
MHDA- 1999/08/04 00:01
CRDT- 1999/08/04 00:00
PHST- 1999/08/04 00:00 [pubmed]
PHST- 1999/08/04 00:01 [medline]
PHST- 1999/08/04 00:00 [entrez]
AID - 10.1073/pnas.96.16.9391 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9391-6. doi: 10.1073/pnas.96.16.9391.