101. Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel
- Author
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Mark A Zaydman, Marina A Kasimova, Kelli McFarland, Zachary Beller, Panpan Hou, Holly E Kinser, Hongwu Liang, Guohui Zhang, Jingyi Shi, Mounir Tarek, and Jianmin Cui
- Subjects
ion channel ,voltage-dependent gating ,electromechanical coupling ,accessory subunit ,KCNE ,KCNQ ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.
- Published
- 2014
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