PMID- 19590188
OWN - NLM
STAT- MEDLINE
DCOM- 20091005
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 24
IP  - 1-2
DP  - 2009
TI  - Long QT syndrome-associated mutations in the voltage sensor of I(Ks) channels.
PG  - 11-6
LID - 10.1159/000227828 [doi]
AB  - The plateau phase of the ventricular action potential is the result of balanced 
      Ca2+ influx and K+ efflux. The action potential is finally terminated by 
      repolarising K+ currents. Under beta-adrenergic stimulation the slowly activating 
      component of the human cardiac delayed rectifier K+ current I(Ks) provides the 
      major repolarising component. I(Ks) channels are heteromeric channels composed of 
      KCNQ1 and KCNE1. Mutations in the voltage sensor S4 of KCNQ1 are associated with 
      long-QT syndrome 1 (LQTS1). Here, we study the effects of the mutations S225L, 
      I235N and L239P located in S4. The respective channels were expressed in Xenopus 
      oocytes and analyzed by dual electrode voltage clamp. As a result all mutants 
      shifted the voltage dependence of activation to the right and reduced the voltage 
      dependence of deactivation kinetics. The activation kinetics were differently 
      affected in homomeric mutant channels compared to wild type KCNQ1. All three 
      mutations reduced KCNQ1/KCNE1 channel currents in a dominant-negative manner when 
      the mutants were coexpressed with wt subunits suggesting reduced I(Ks) as the 
      molecular basis of LQT1.
CI  - 2009 S. Karger AG, Basel.
FAU - Henrion, Ulrike
AU  - Henrion U
AD  - Department of Physiology I, University of Tuebingen, Tuebingen, Germany.
FAU - Strutz-Seebohm, Nathalie
AU  - Strutz-Seebohm N
FAU - Duszenko, Michael
AU  - Duszenko M
FAU - Lang, Florian
AU  - Lang F
FAU - Seebohm, Guiscard
AU  - Seebohm G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090701
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (KCNE1 protein, human)
RN  - 0 (KCNQ1 Potassium Channel)
RN  - 0 (KCNQ1 protein, human)
RN  - 0 (Potassium Channels, Voltage-Gated)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Electrophysiological Phenomena
MH  - Humans
MH  - KCNQ1 Potassium Channel/genetics/*physiology
MH  - Long QT Syndrome/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Oocytes/metabolism
MH  - Potassium Channels, Voltage-Gated/physiology
MH  - Protein Structure, Tertiary
MH  - Sequence Homology, Amino Acid
MH  - Xenopus laevis
EDAT- 2009/07/11 09:00
MHDA- 2009/10/06 06:00
CRDT- 2009/07/11 09:00
PHST- 2009/04/23 00:00 [accepted]
PHST- 2009/07/11 09:00 [entrez]
PHST- 2009/07/11 09:00 [pubmed]
PHST- 2009/10/06 06:00 [medline]
AID - 000227828 [pii]
AID - 10.1159/000227828 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2009;24(1-2):11-6. doi: 10.1159/000227828. Epub 2009 Jul 1.