) Background: sudden cardiac death is an important cause of cardiovascular mortality in the United States. The long QT syndrome (LQT) is an inherited disorder associated with ventricular arrhythmias and sudden death. Mutations in the gene KVLQT1 cause the most common form of inherited LQT. KvLQT1 proteins coassemble with a regulatory subunit, minK, to form the slowly activating cardiac delayed rectifier (Iks) channel. Iks is an important modulator of cardiac repolarization, and as such, reductions in Iks may promote arrhythmia susceptibility. The goals of this proposal are: (1) To characterize the molecular interactions between Iks channel subunits and (2) To define the molecular pathogenesis of LQT-associated mutations in KVLQT1 and hminK. The studies will be performed using cloned human minK and KvLQT1 proteins heterologously expressed in Xenopus oocytes. Significance: Insight into the molecular pathogenesis of LQT and the molecular mechanisms of K+ channel regulation will facilitate development of novel treatment strategies for life-threatening arrhythmias. Environment: The University of Utah is a preeminent research institution in the field of cardiac ion channel research and the molecular genetics of LQT.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003816-04
Application #
6388448
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (F1))
Program Officer
Commarato, Michael
Project Start
1998-06-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
4
Fiscal Year
2001
Total Cost
$123,930
Indirect Cost
Name
University of Utah
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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