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

Cardiac Ion Channels - Pharmacology of Sotalol

CiPA PE CE Pharmacology SotalolIcon CE    CardioExcyte 96 and   icon sp96   SyncroPatch 384PE 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 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 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   icon pl   Patchliner   Icon CE   CardioExcyte 96 application note   logo pdf   (2.3 MB)

Publications

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 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 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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