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Update on the Slow Delayed Rectifier Potassium Current (IKs): Role in Modulating Cardiac Function

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Abstract:

The slow delayed rectifier current (IKs) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. IKs channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of IKs channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of IKs channel in modulating cardiac function and donate some instructions to the progression of IKs blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of IKs.





Keywords: 673; Chromanol293B; HMR1556; IKs; IKs activator; KCNE1; KCNQ1; KvLQT1; L-768; The slow delayed rectifier potassium current; antiarrhythmic agents; cardiac arrhythmia

Document Type: Research Article

DOI: https://doi.org/10.2174/092986712799462595

Publication date: 2012-03-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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