• KV7.1

    Analysis of KV7.1/KCNE co-expressed channels on the Patchliner

KV7.1 | KVLQT1 | KQT Related Potassium Channel Member 1

Family:
Potassium channels

Subgroups:
Shaker (KV1.1–KV1.8), Shab (KV2.1-KV2.2), Shaw (KV3.1–KV3.4), Shal (KV4.1–KV4.3), KQT like (KV7.1–KV7.5), Eag related (KV10.1-KV10.2), Erg related (KV11.1–KV11.3), Elk related (KV12.1)

Topology:
Contains six transmembrane domains (S1–S6), four single subunits form a pore, homotetramers and heterotetramers are possible.

KV7.1 Background Information

KV7.1, also known as KVLQT1, is a voltage-gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among other tissues. It induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current and promotes also a delayed voltage activated potassium current showing outward rectification characteristic. In the cardiac cells, KV7.1 mediates the IKs (or slow delayed rectifying K+) current that contributes to the repolarization of the cell, terminating the cardiac action potential and thereby the heart's contraction. The gene product can form heteromers with KCNE1 (minK), KCNE2, KCNE3 (miRP2), KCNE4, KCNE5 and KCNQ5. General mutations in KV7.1 have been known to cause a decrease in this slow delayed potassium rectifier current, longer cardiac action potentials, and a tendency to have tachyarrhythmias in the heart.

Gene:
KCNQ1

Human Protein:
P51787

Tissue:
Heart, pancreas, inner ear, stomach, colon

Function/ Application:
Contributes to the repolarization of the cardiomyocytes, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions and maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion

Pathology:
Beckwith-Wiedemann syndrome, cancer, Long QT syndrome (LQT1, also known as Romano-Ward syndrome), Jervell syndrome, Lange-Nielsen syndrome, Short QT syndrome, Familial Atrial Fibrillation, hyperinsulinemic hypoglycaemia, abnormality of the ear, accelerated skeletal maturation, adrenocortical cytomegaly

Interaction:
Forms heterotetramers with KCNE1 (minK), KCNE2, KCNE3 (miRP2), KCNE4, KCNE5, KCNQ5 and associates with PRKACA, PPP1CA, AKAP9, Serine/threonine-protein kinases SGK, Calmodulin 1, 2, 3

Modulator:
4-AP, bepridil, indapamide 2, Oxotremorine-M, ezogabine, mefenamic acid, E-4031, linopirdine dihydrochloride, agitoxin 2

Assays:
Patch Clamp: whole cell

Recommended Reviews:
Gutman et al. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 57(4):473-508

Data and Applications

KV7.1 (KVLQT) - current-voltage relationship

IKs ApconiX PL IVicon pl   Patchliner data and applications: 
Data kindly provided by ApconiX, UK

KCNQ1/KCNE1 expressed in CHO cells was activated using increasing voltage steps. Shown are traces from an example cell and the normalized current-voltage plot for an average of 8 cells. The IKs current mediated by KCNQ1/KCNE1 started to activate at approximately -20 mV and increased with each voltage step (increment 10 mV). The normalized IV curve was fit using a Boltzmann equation revealing a Vhalf of activation of 25 mV.

KCNQ1/KCNE1 - block by Chromanol 293B

IKs PL Chromanolicon pl   Patchliner data and applications: 
Data kindly provided by ApconiX, UK

KCNQ1/KCNE1 expressed in CHO cells was activated using a 2 s voltage step to 40 mV and blocked by increasing concentrations of chromanol 293B.  Shown are traces from an example cell in the absence and presence of chromanol 293B and the normalized concentration response curve for an average of 6 cells. The curve was fit with a Hill equation revealing an IC50 = 2.8 ± 0.9 μM (n = 6). 

Cardiac Ion Channels - Pharmacology of Sotalol

CiPA PE CE Pharmacology SotalolIcon CE    CardioExcyte 96 and   icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.

The image on the left hand side displays the results of the blocking effect of Sotalol on hERG. The result is in good agreement with manual patch clamp data (Crumb et al., 2016). The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 10 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility measurements.

KV7.1 (KVLQT) - Dose-response curve

icon sp96   170922 KV7.1 Data SyncroPatch384PESyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing KV7.1/KCNE (KVLQT/minK) current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Using the perforated patch methodology (Escin) in combination with multi-hole chips (4 holes per well), stably transfected cells were measured on the SyncroPatch 384PE. The IC50 value of Chromanol 293B was determined as 3.82 µM. The success rate of valuable data for the analysis was 100%. 

Application Notes

Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note   logo pdf   (1.3 MB)
Cells were kindly provided by Charles River.

Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i)   icon pl   Patchliner   Icon CE   CardioExcyte 96 application note   logo pdf   (2.3 MB)

Posters

2018 - ハイスループット自動パッチクランプ システムの進展:安全性薬理試験への応用

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) poster, JSPS Meeting 2018  logo pdf   (2.3 MB)

2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and   icon pl   Patchliner poster, BPS Meeting 2017  logo pdf   (1.7 MB)

2015 - High Throughput Automated Patch Clamp of Ion Channels Important in Cardiac Safety and Drug Discovery

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) poster, Chantest Meeting 2015   logo pdf   (1.9 MB)

Webinars & Presentations

28.07.2015 | Webinar: High Throughput and High Fidelity: Automated Patch Clamp in Screening and Research

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and   icon pl   Patchliner 

The webinar covers the use of the Patchliner and the SyncroPatch 384/768PE for characterization of ion channels and screening of ion channel active compounds.

2018 - HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner

icon sp96  SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i),   icon pl   Patchliner and   Icon CE   CardioExcyte 96 Oral Presentation

Presenter: 
Tim Strassmaier, Nanion Technologies Inc. USA
Source:
Webinar: "CiPA study: Bridging ion channel and myocyte data", September 12, 2018

2017 - HTS in Cardiac Safety

Icon CE   CardioExcyte 96 presentation (slide deck)   logo pdf   (4.0 MB)

Publications

2019 - Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2

icon pap   Port-a Patch Publication in EP Europace (2019)

Authors:
Bodi I., Sorge J., Castiglione A., Glatz S.M., Wuelfers E.M., Franke G., Perez-Feliz S., Koren G., Zehender M., Bugger H., Seemann G., Brunner M., Bode C., Odening K.E.

2019 - A Kinetic Map of the Homomeric Voltage-Gated Potassium Channel (Kv) Family

 icon pl   Patchliner publication in Frontiers in Cellular Neuroscience (2019)

Authors:
Ranjan R., Logette E., Marani M., Herzog M., Tâche V., Scantamburlo E., Buchillier V., Markram H.

2018 - Reconstitution and Electrophysiological Characterization of Ion Channels in Lipid Bilayers

icon pap   Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Current Protocols in Pharmacology (2018)

Authors:
Klaerke D.A., de los Angeles Tejada M., Grøsfjeld Christensen V., Lassen M., Amstrup Pedersen P., Calloe K.

2018 - High-Throughput Functional Evaluation of KCNQ1 Decrypts Variants of Unknown Significance

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) article in Circulation: Genomic and Precision Medicine (2018)

Authors:
Vanoye C.G., Desai R.R., Fabre K.L., Gallagher S.L., Potet F., DeKeyser J.M., Macaya D., Meiler J, Sanders C.R, and George Jr. A.L.

2014 - New strategies in ion channel screening for drug discovery: are there ways to improve its productivity?

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Laboratory Automation (2014)

Authors: 
Farre C., Fertig N.

2013 - Differential Effects of the β‐Adrenoceptor Blockers Carvedilol and Metoprolol on SQT1‐ and SQT2‐Mutant Channels

icon pap   Port-a-Patch publication in Journal of Cardiovascular Electrophysiology (2013)

Authors: 
Bodi I., Franke G., Pantulu N.D., Wu K., Perez-Feliz S., Bode C., Zehender M., Zur Hausen A., Brunner M., Odening K.

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