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
KCNQ1/KCNE1 - current-voltage relationship
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
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
CardioExcyte 96 and 
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
SyncroPatch 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"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note 
(1.3 MB)
Cells were kindly provided by Charles River.
Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) Patchliner CardioExcyte 96 application note (2.3 MB)
Publications
2019 - Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2
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
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
Port-a-Patch and 
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
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?
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
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.