) 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.
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| Piper, David R; Hinz, William A; Tallurri, Chandra K et al. (2005) Regional specificity of human ether-a'-go-go-related gene channel activation and inactivation gating. J Biol Chem 280:7206-17 |
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| Tristani-Firouzi, Martin; Chen, Jun; Sanguinetti, Michael C (2002) Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels. J Biol Chem 277:18994-9000 |
