PMID- 10228147
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 9
DP  - 1999 May 4
TI  - Two pacemaker channels from human heart with profoundly different activation
      kinetics.
PG  - 2323-9
AB  - Cardiac pacemaking is produced by the slow diastolic depolarization phase of the 
      action potential. The hyperpolarization-activated cation current (If) forms an
      important part of the pacemaker depolarization and consists of two kinetic
      components (fast and slow). Recently, three full-length cDNAs encoding
      hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN1-3) 
      have been cloned from mouse brain. To elucidate the molecular identity of cardiac
      pacemaker channels, we screened a human heart cDNA library using a highly
      conserved neuronal HCN channel segment and identified two cDNAs encoding HCN
      channels. The hHCN2 cDNA codes for a protein of 889 amino acids. The HCN2 gene is
      localized on human chromosome 19p13.3 and contains eight exons spanning
      approximately 27 kb. The second cDNA, designated hHCN4, codes for a protein of
      1203 amino acids. Northern blot and PCR analyses showed that both hHCN2 and hHCN4
      are expressed in heart ventricle and atrium. When expressed in HEK 293 cells,
      either cDNA gives rise to hyperpolarization-activated cation currents with the
      hallmark features of native If. hHCN2 and hHCN4 currents differ profoundly from
      each other in their activation kinetics, being fast and slow, respectively. We
      thus conclude that hHCN2 and hHCN4 may underlie the fast and slow component of
      cardiac If, respectively.
FAU - Ludwig, A
AU  - Ludwig A
AD  - Institut fur Pharmakologie und Toxikologie der Technischen Universitat Munchen,
      Biedersteiner Strasse 29, 80802 Munchen, Germany.
FAU - Zong, X
AU  - Zong X
FAU - Stieber, J
AU  - Stieber J
FAU - Hullin, R
AU  - Hullin R
FAU - Hofmann, F
AU  - Hofmann F
FAU - Biel, M
AU  - Biel M
LA  - eng
SI  - GENBANK/AJ012582
SI  - GENBANK/AJ132429
SI  - GENBANK/AJ133727
SI  - GENBANK/AJ133728
SI  - GENBANK/AJ133729
SI  - GENBANK/AJ133730
SI  - GENBANK/AJ133731
SI  - GENBANK/AJ133732
SI  - GENBANK/AJ133733
SI  - GENBANK/AJ133734
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Cyclic Nucleotide-Gated Cation Channels)
RN  - 0 (HCN2 protein, human)
RN  - 0 (HCN4 protein, human)
RN  - 0 (Hcn2 protein, mouse)
RN  - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels)
RN  - 0 (Ion Channels)
RN  - 0 (Muscle Proteins)
RN  - 0 (Potassium Channels)
SB  - IM
MH  - *Biological Clocks
MH  - Chromosomes, Human, Pair 19
MH  - Cloning, Molecular
MH  - Cyclic Nucleotide-Gated Cation Channels
MH  - Electrophysiology
MH  - Heart Atria
MH  - Heart Ventricles
MH  - Humans
MH  - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
MH  - *Ion Channel Gating
MH  - Ion Channels/genetics/*metabolism
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - *Muscle Proteins
MH  - Myocardium/*metabolism
MH  - Potassium Channels
MH  - Sequence Analysis, DNA
MH  - Tissue Distribution
PMC - PMC1171315
EDAT- 1999/05/06 00:00
MHDA- 1999/05/06 00:01
CRDT- 1999/05/06 00:00
PHST- 1999/05/06 00:00 [pubmed]
PHST- 1999/05/06 00:01 [medline]
PHST- 1999/05/06 00:00 [entrez]
AID - 10.1093/emboj/18.9.2323 [doi]
PST - ppublish
SO  - EMBO J. 1999 May 4;18(9):2323-9. doi: 10.1093/emboj/18.9.2323.