PMID- 10400998
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20220129
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and
      trafficking in long QT syndrome.
PG  - 1499-507
AB  - Mutations in the minK gene KCNE1 have been linked to the LQT5 variant of human
      long QT syndrome. MinK assembles with KvLQT1 to produce the slow delayed
      rectifier K+ current IKs and may assemble with HERG to modulate the rapid delayed
      rectifier IKr. We used electrophysiological and immunocytochemical methods to
      compare the cellular phenotypes of wild-type minK and four LQT5 mutants
      co-expressed with KvLQT1 in Xenopus oocytes and HERG in HEK293 cells. We found
      that three mutants, V47F, W87R and D76N, were expressed at the cell surface,
      while one mutant, L51H, was not. Co-expression of V47F and W87R with KvLQT1
      produced IKs currents having altered gating and reduced amplitudes compared with 
      WT-minK, co-expression with L51H produced KvLQT1 current rather than IKs and
      co-expression with D76N suppressed KvLQT1 current. V47F increased HERG current
      but to a lesser extent than WT-minK, while L51H and W87R had no effect and D76N
      suppressed HERG current markedly. Thus, V47F interacts with both KvLQT1 and HERG,
      W87R interacts functionally with KvLQT1 but not with HERG, D76N suppresses both
      KvLQT1 and HERG, and L51H is processed improperly and interacts with neither
      channel. We conclude that minK is a co-factor in the expression of both IKs and
      IKr and propose that clinical manifestations of LQT5 may be complicated by
      differing effects of minK mutations on KvLQT1 and HERG.
FAU - Bianchi, L
AU  - Bianchi L
AD  - The Rammelkamp Center for Education and Research, MetroHealth Campus, Case
      Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109-1998,
      USA,
FAU - Shen, Z
AU  - Shen Z
FAU - Dennis, A T
AU  - Dennis AT
FAU - Priori, S G
AU  - Priori SG
FAU - Napolitano, C
AU  - Napolitano C
FAU - Ronchetti, E
AU  - Ronchetti E
FAU - Bryskin, R
AU  - Bryskin R
FAU - Schwartz, P J
AU  - Schwartz PJ
FAU - Brown, A M
AU  - Brown AM
LA  - eng
GR  - 1058/TI_/Telethon/Italy
GR  - HL55404/HL/NHLBI NIH HHS/United States
GR  - HL36930/HL/NHLBI NIH HHS/United States
GR  - NS23877/NS/NINDS 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  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Cation Transport Proteins)
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))
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Substitution
MH  - Animals
MH  - *Cation Transport Proteins
MH  - Cell Line
MH  - *DNA-Binding Proteins
MH  - ERG1 Potassium Channel
MH  - Electrophysiology
MH  - Ether-A-Go-Go Potassium Channels
MH  - Family Health
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Long QT Syndrome/*genetics/physiopathology
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Mutation
MH  - Oocytes
MH  - Patch-Clamp Techniques
MH  - Pedigree
MH  - Potassium Channels/*genetics
MH  - *Potassium Channels, Voltage-Gated
MH  - *Trans-Activators
MH  - Transcriptional Regulator ERG
MH  - Xenopus
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - ddc166 [pii]
AID - 10.1093/hmg/8.8.1499 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1499-507. doi: 10.1093/hmg/8.8.1499.