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 Ceramide modulates HERG potassium channel gating by translocation into lipid rafts

2010 ◽  
Vol 299 (1) ◽  
pp. C74-C86 ◽  
Author(s):  
Sindura B. Ganapathi ◽  
Todd E. Fox ◽  
Mark Kester ◽  
Keith S. Elmslie
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Lipid Rafts ◽  
Negative Impact ◽  
Cardiac Action Potential ◽  
Cholesterol Depletion ◽  
Cardiac Action ◽  
Herg Channels ◽  
The Impact ◽  
Action Potential Repolarization

Human ether-à-go-go-related gene (HERG) potassium channels play an important role in cardiac action potential repolarization, and HERG dysfunction can cause cardiac arrhythmias. However, recent evidence suggests a role for HERG in the proliferation and progression of multiple types of cancers, making it an attractive target for cancer therapy. Ceramide is an important second messenger of the sphingolipid family, which due to its proapoptotic properties has shown promising results in animal models as an anticancer agent . Yet the acute effects of ceramide on HERG potassium channels are not known. In the present study we examined the effects of cell-permeable C6-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C6-ceramide (10 μM) reversibly inhibited HERG channel current (IHERG) by 36 ± 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage relationship (Δ V1/2 = −8 ± 0.5 mV) and increased the deactivation rate (43 ± 3% for τfast and 51 ± 3% for τslow). Mechanistically, ceramide recruited HERG channels within caveolin-enriched lipid rafts. Cholesterol depletion and repletion experiments and mathematical modeling studies confirmed that inhibition and gating effects are mediated by separate mechanisms. The ceramide-induced hyperpolarizing gating shift (raft mediated) could offset the impact of inhibition (raft independent) during cardiac action potential repolarization, so together they may nullify any negative impact on cardiac rhythm. Our results provide new insights into the effects of C6-ceramide on HERG channels and suggest that C6-ceramide can be a promising therapeutic for cancers that overexpress HERG.

scholarly journals Novel intramolecular photoinduced electron transfer-based probe for the Human Ether-a-go-go-Related Gene (hERG) potassium channel

The Analyst ◽  
2015 ◽  
Vol 140 (24) ◽  
pp. 8101-8108 ◽  
Author(s):  
Zhenzhen Liu ◽  
Yubin Zhou ◽  
Lupei Du ◽  
Minyong Li
Keyword(s):  
Electron Transfer ◽  
Potassium Channel ◽  
Photoinduced Electron Transfer ◽  
Herg Channel ◽  
Good Activity ◽  
Related Gene ◽  
Careful Evaluation ◽  
Promising Application

A novel conformation-mediated intramolecular photoinduced electron transfer fluorogenic system based-on naphthalimide fluorophore was established for hERG potassium channel herein. After careful evaluation, probe N4 and N6 showed good activity and may have a promising application in hERG channel imaging and drug cardiotoxicity evaluation.

Regulation of the human ether-a-go-go-related gene (hERG) potassium channel by Nedd4 family interacting proteins (Ndfips)

2015 ◽  
Vol 472 (1) ◽  
pp. 71-82 ◽  
Author(s):  
Yudi Kang ◽  
Jun Guo ◽  
Tonghua Yang ◽  
Wentao Li ◽  
Shetuan Zhang
Keyword(s):  
Potassium Channel ◽  
Precursor Cell ◽  
K Channel ◽  
Neural Precursor ◽  
Cardiac Repolarization ◽  
Interacting Proteins ◽  
Neural Precursor Cell ◽  
Related Gene ◽  
Cellular Compartments ◽  
Herg Channels

The human ether-a-go-go-related gene (hERG)-encoded K+ channel is critical for cardiac repolarization. In the present study, we demonstrate that the E3 ubiquitin (Ub) ligase neural precursor cell expressed developmentally down-regulated protein 4-2 (Nedd4-2) is directed to specific cellular compartments by Nedd4 family-interacting proteins (Ndfips) to selectively target the mature hERG channels for degradation.

scholarly journals NBD-Based Environment-Sensitive Fluorescent Probes for the Human Ether-a-Go-Go–Related Gene Potassium Channel

2021 ◽  
Vol 8 ◽  
Author(s):  
Qi Li ◽  
Lijuan Chai ◽  
Gaopan Dong ◽  
Xiaomeng Zhang ◽  
Lupei Du
Keyword(s):  
Fluorescent Proteins ◽  
Fluorescent Labeling ◽  
Herg Channel ◽  
Screening System ◽  
Related Gene ◽  
Careful Evaluation ◽  
Economical Method ◽  
High Affinity ◽  
Herg Channels

Three environment-sensitive probes were developed for the hERG channel based on the nitrobenzoxadiazole fluorophore herein. After careful evaluation, probes M1 and M3 were found to have a high affinity for imaging the hERG channel in the cell-based experiment. Compared with other fluorescent labeling technologies (such as fluorescent proteins), these probes afford a convenient and economical method to determine hERG channel in vitro and in cellulo. Therefore, these probes are expected to be applicable for usage in physiological and pathological studies of hERG channels and have the potential to establish a screening system for hERG channels.

scholarly journals Increased Risk of Arrhythmic Events in Long-QT Syndrome With Mutations in the Pore Region of the Human Ether-a-go-go–Related Gene Potassium Channel

Circulation ◽  
2002 ◽  
Vol 105 (7) ◽  
pp. 794-799 ◽  
Author(s):  
Arthur J. Moss ◽  
Wojciech Zareba ◽  
Elizabeth S. Kaufman ◽  
Eric Gartman ◽  
Derick R. Peterson ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Long Qt Syndrome ◽  
Related Gene ◽  
Long Qt ◽  
Pore Region ◽  
Increased Risk ◽  
Qt Syndrome

Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart

2002 ◽  
Vol 283 (1) ◽  
pp. H126-H138 ◽  
Author(s):  
Melissa R. Finley ◽  
Yan Li ◽  
Fei Hua ◽  
James Lillich ◽  
Kathy E. Mitchell ◽  
...  
Keyword(s):  
Cardiac Arrhythmias ◽  
Molecular Basis ◽  
Cardiac Tissue ◽  
Delayed Rectifier ◽  
Related Gene ◽  
Rt Pcr ◽  
Delayed Rectifier Current ◽  
Cardiac Action ◽  
Qt Syndrome ◽  
Α Subunits

In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 α-subunits, in association with KCNE β-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.

Early Afterdepolarization Abolished by Potassium Channel Opener in a Patient with Idiopathic Long QT Syndrome

1995 ◽  
Vol 6 (4) ◽  
pp. 279-282 ◽  
Author(s):  
TETSUYA SATO ◽  
YOSHIKI HATA ◽  
MIKA YAMAMOTO ◽  
HIROSHI MORITA ◽  
KOZO MIZUO ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Long Qt Syndrome ◽  
Potassium Channel Opener ◽  
Long Qt ◽  
Channel Opener ◽  
Early Afterdepolarization ◽  
Qt Syndrome
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