Refining Insights into High-Affinity Drug Binding to the Human Ether-à-go-go-Related Gene Potassium Channel: Fig. 1.

2008 ◽  
Vol 73 (6) ◽  
pp. 1592-1595 ◽  
Author(s):  
Jules C. Hancox ◽  
Andrew F. James
Keyword(s):  
Potassium Channel ◽  
Drug Binding ◽  
Related Gene ◽  
High Affinity

Drug Binding to the Inactivated State Is Necessary but Not Sufficient for High-Affinity Binding to Human Ether-à-go-go-Related Gene Channels

2008 ◽  
Vol 74 (5) ◽  
pp. 1443-1452 ◽  
Author(s):  
Mark J. Perrin ◽  
Philip W. Kuchel ◽  
Terence J. Campbell ◽  
Jamie I. Vandenberg
Keyword(s):  
Drug Binding ◽  
Affinity Binding ◽  
Related Gene ◽  
High Affinity Binding ◽  
High Affinity

How to Fluorescently Label the Potassium Channel: A Case in hERG

2020 ◽  
Vol 27 (18) ◽  
pp. 3046-3054
Author(s):  
Xiaomeng Zhang ◽  
Beilei Wang ◽  
Zhenzhen Liu ◽  
Yubin Zhou ◽  
Lupei Du
Keyword(s):  
Potassium Channel ◽  
Herg Channel ◽  
Pore Channel ◽  
Design Rationale ◽  
Related Gene ◽  
Open Conformation ◽  
Cardiac Action ◽  
Qt Syndrome ◽  
Herg Channels ◽  
Action Potential Repolarization

hERG (Human ether-a-go-go-related gene) potassium channel, which plays an essential role in cardiac action potential repolarization, is responsible for inherited and druginduced long QT syndrome. Recently, the Cryo-EM structure capturing the open conformation of hERG channel was determined, thus pushing the study on hERG channel at 3.8 Å resolution. This report focuses primarily on summarizing the design rationale and application of several fluorescent probes that target hERG channels, which enables dynamic and real-time monitoring of potassium pore channel affinity to further advance the understanding of the channels.

scholarly journals A mechanism for the proarrhythmic effects of cisapride (Propulsid): high affinity blockade of the human cardiac potassium channel HERG

FEBS Letters ◽  
1997 ◽  
Vol 417 (1) ◽  
pp. 28-32 ◽  
Author(s):  
David Rampe ◽  
Mary-Louise Roy ◽  
Adrienne Dennis ◽  
Arthur M Brown
Keyword(s):  
Potassium Channel ◽  
High Affinity

Circadian changes of ether-a-go-go-related-gene (Erg) potassium channel transcripts in the rat pancreas and β-cell

2007 ◽  
Vol 64 (6) ◽  
pp. 768-780 ◽  
Author(s):  
E. Mühlbauer ◽  
I. Bazwinsky ◽  
S. Wolgast ◽  
A. Klemenz ◽  
E. Peschke
Keyword(s):  
Potassium Channel ◽  
Related Gene ◽  
Β Cell ◽  
Rat Pancreas ◽  
Circadian Changes

scholarly journals Comparative Effects of Liensinine and Neferine on the Human Ether-a-go-go-related Gene Potassium Channel and Pharmacological Activity Analysis

2012 ◽  
Vol 29 (3-4) ◽  
pp. 431-442 ◽  
Author(s):  
Zeng-Xiang Dong ◽  
Xin Zhao ◽  
Dong-Fang Gu ◽  
Yuan-Qi Shi ◽  
Jia Zhang ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Pharmacological Activity ◽  
Activity Analysis ◽  
Related Gene

scholarly journals Two Ways To Convert a Low-Affinity Potassium Channel to High Affinity: Control of Bacillus subtilis KtrCD by Glutamate

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
Larissa Krüger ◽  
Christina Herzberg ◽  
Robert Warneke ◽  
Anja Poehlein ◽  
Janina Stautz ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Potassium Channel ◽  
Living Cell ◽  
Potassium Uptake ◽  
Selectivity Filter ◽  
Uptake System ◽  
Content Type ◽  
Apparent Affinity ◽  
High Affinity ◽  
External Potassium

ABSTRACT Potassium and glutamate are the major cation and anion, respectively, in every living cell. Due to the high concentrations of both ions, the cytoplasm of all cells can be regarded as a potassium glutamate solution. This implies that the concentrations of both ions need to be balanced. While the control of potassium uptake by glutamate is well established for eukaryotic cells, much less is known about the mechanisms that link potassium homeostasis to glutamate availability in bacteria. Here, we have discovered that the availability of glutamate strongly decreases the minimal external potassium concentration required for the highly abundant Bacillus subtilis potassium channel KtrCD to accumulate potassium. In contrast, the inducible KtrAB and KimA potassium uptake systems have high apparent affinities for potassium even in the absence of glutamate. Experiments with mutant strains revealed that the KtrD subunit responds to the presence of glutamate. For full activity, KtrD synergistically requires the presence of the regulatory subunit KtrC and of glutamate. The analysis of suppressor mutants of a strain that has KtrCD as the only potassium uptake system and that experiences severe potassium starvation identified a mutation in the ion selectivity filter of KtrD (Gly282 to Val) that similarly results in a strongly glutamate-independent increase of the apparent affinity for potassium. Thus, this work has identified two conditions that increase the apparent affinity of KtrCD for potassium, i.e., external glutamate and the acquisition of a single point mutation in KtrD. IMPORTANCE In each living cell, potassium is required for maintaining the intracellular pH and for the activity of essential enzymes. Like most other bacteria, Bacillus subtilis possesses multiple low- and high-affinity potassium uptake systems. Their activity is regulated by the second messenger cyclic di-AMP. Moreover, the pools of the most abundant ions potassium and glutamate must be balanced. We report two conditions under which the low-affinity potassium channel KtrCD is able to mediate potassium uptake at low external potassium concentrations: physiologically, the presence of glutamate results in a severely increased potassium uptake. Moreover, this is achieved by a mutation affecting the selectivity filter of the KtrD channel. These results highlight the integration between potassium and glutamate homeostasis in bacteria.

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