Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5

Abstract

The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (IKur) current in human cells, has a crucial role in atrial fibrillation. Therefore, the design of selective Kv1.5 modulators is essential for the treatment of pathophysiological conditions involving Kv1.5 activity. This review summarizes the progress of molecular structures and the functionality of different types of Kv1.5 modulators, with a focus on clinical cardiovascular drugs and a number of active natural products, through a summarization of 96 compounds currently widely used. Furthermore, we also discuss the contributions of Kv1.5 and the regulation of the structure-activity relationship (SAR) of synthetic Kv1.5 inhibitors in human pathophysiology. SAR analysis is regarded as a useful strategy in structural elucidation, as it relates to the characteristics that improve compounds targeting Kv1.5. Herein, we present previous studies regarding the structural, pharmacological, and SAR information of the Kv1.5 modulator, through which we can assist in identifying and designing potent and specific Kv1.5 inhibitors in the treatment of diseases involving Kv1.5 activity.

Methods of prolonging the effect of caudal block in children

“…Bupivacaine is often a racemic combination of R- and S-enantiomers because of chiral carbon atoms; ropivacaine is the first local anesthetic to be synthesized as a pure S-enantiomer. Because the S-enantiomer has a lower affinity for sodium and potassium (hKvl.5) cardiac channels than the R(+)-enantiomer does for these cardiac channels ( 5 ), ropivacaine has a wider margin of safety than bupivacaine ( 6 , 7 ). It is more slowly absorbed systematically from the caudal epidural space, and has a lower potential for adverse effects on the central nervous system and the cardiovascular system ( 4 , 8 ).…”

Genetic polymorphisms associated with the development of arrhythmic type of cardiovascular events

“…Потенциалзависимые калиевые каналы представляют более сложный класс ионных каналов, ориентируясь на структурную и функциональную стороны. Основная их задача состоит в регуляции процессов высвобождения нейромедиаторов, возбудимости нейронов, эпителиального транспорта электролитов; генерации и контроля частоты сердечных сокращений, обеспечение согласованной работы гладких мышц [44]. Белок KCNQ1, являясь чле-ном подсемейства Q-зависимых каналов, взаимодействует с белками семейства KCNE (KCNE1, KCNE2, KCNE3, KCNE5) [45].…”

Linked biaromatic compounds as cardioprotective agents

“…The selective presence of I Kur in the atria makes it an interesting target for atria selective therapy, whereby inhibition of I Kur would prolong the APD in the atria but not the ventricles, which allows you to avoid the risk of inducing QT prolongation and ventricular arrhythmias. [ 91,158,159 ]…”

“…First of all, the linker contains a phenyl prolongation and ventricular arrhythmias. [91,158,159] LBCs were often used by researchers for the design of Kv1.5 blockers. Among them, a large number of effective cardioprotective compounds have been identified.…”