PMID- 10219239
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 97
IP  - 2
DP  - 1999 Apr 16
TI  - MiRP1 forms IKr potassium channels with HERG and is associated with cardiac
      arrhythmia.
PG  - 175-87
AB  - A novel potassium channel gene has been cloned, characterized, and associated
      with cardiac arrhythmia. The gene encodes MinK-related peptide 1 (MiRP1), a small
      integral membrane subunit that assembles with HERG, a pore-forming protein, to
      alter its function. Unlike channels formed only with HERG, mixed complexes
      resemble native cardiac IKr channels in their gating, unitary conductance,
      regulation by potassium, and distinctive biphasic inhibition by the class III
      antiarrhythmic E-4031. Three missense mutations associated with long QT syndrome 
      and ventricular fibrillation are identified in the gene for MiRP1. Mutants form
      channels that open slowly and close rapidly, thereby diminishing potassium
      currents. One variant, associated with clarithromycin-induced arrhythmia,
      increases channel blockade by the antibiotic. A mechanism for acquired arrhythmia
      is revealed: genetically based reduction in potassium currents that remains
      clinically silent until combined with additional stressors.
FAU - Abbott, G W
AU  - Abbott GW
AD  - Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University
      School of Medicine, New Haven, Connecticut 06536, USA.
FAU - Sesti, F
AU  - Sesti F
FAU - Splawski, I
AU  - Splawski I
FAU - Buck, M E
AU  - Buck ME
FAU - Lehmann, M H
AU  - Lehmann MH
FAU - Timothy, K W
AU  - Timothy KW
FAU - Keating, M T
AU  - Keating MT
FAU - Goldstein, S A
AU  - Goldstein SA
LA  - eng
SI  - GENBANK/AF071002
SI  - GENBANK/AF071003
SI  - GENBANK/AF076531
SI  - GENBANK/AF076532
SI  - GENBANK/AF076533
GR  - MO1-RR00064/RR/NCRR NIH HHS/United States
GR  - P50-HL52338/HL/NHLBI NIH HHS/United States
GR  - R01-HL46401/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (KCNH6 protein, human)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - 0 (potassium channel protein I(sk))
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arrhythmias, Cardiac/etiology/genetics/*metabolism
MH  - Base Sequence
MH  - *Cation Transport Proteins
MH  - Cloning, Molecular
MH  - DNA Primers/genetics
MH  - *DNA-Binding Proteins
MH  - ERG1 Potassium Channel
MH  - Electric Conductivity
MH  - Ether-A-Go-Go Potassium Channels
MH  - Female
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Long QT Syndrome/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Potassium/metabolism
MH  - Potassium Channels/chemistry/genetics/*metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Protein Conformation
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - *Trans-Activators
MH  - Transcriptional Regulator ERG
MH  - Xenopus laevis
EDAT- 1999/04/29 00:00
MHDA- 1999/04/29 00:01
CRDT- 1999/04/29 00:00
PHST- 1999/04/29 00:00 [pubmed]
PHST- 1999/04/29 00:01 [medline]
PHST- 1999/04/29 00:00 [entrez]
AID - S0092-8674(00)80728-X [pii]
AID - 10.1016/s0092-8674(00)80728-x [doi]
PST - ppublish
SO  - Cell. 1999 Apr 16;97(2):175-87. doi: 10.1016/s0092-8674(00)80728-x.