Kir2.1 | Potassium Voltage-Gated Channel Subfamily J Member 2
Family:
Inward-rectifier potassium ion channel
Subgroups:
Seven families channels demonstrate robust inward rectification: Kir1.1; Kir2.1 - Kir2.4; Kir3.1 - Kir3.4, Kir4.1 - Kir4.2; Kir5.1, Kir6.1 - Kir6.2; Kir7.1
Topology:
The channel protein contains two membrane spanning alpha helices denoted as M1 and M2. Four identical subunits form a functional homotetramer, heterotetramers can combine with members of the same subfamily
Kir2.1 Background Information
Kir2.1 is a inward rectifier potassium channel which participates in establishing action potential waveform and excitability of neuronal and muscle tissues.
Gene:
KCNJ2
Human Protein:
UniProt P63252
Tissue:
Heart, peripheral nerves, brain, vascular smooth muscle cells, skeletal muscles, lung, placenta, kidney
Function/ Application:
Participates in establishing action potential waveform and excitability of neuronal and muscle tissues, mediates the IK1 current in the heart
Pathology:
Andersen-Tawil syndrome, Short QT syndrome 3, Autosomal dominant inheritance, Bidirectional ventricular ectopy, Blepharophimosis, Brachydactyly syndrome, Long QT syndrome 7 (LQT7), Atrial fibrillation familial, 9 (ATFB9), PiP2
Interaction:
Forms heterodimers with Kir2.2 and Kir4.1. Interacts with Kir2.3, DLG4, DLG1, CASK, APBA1, interleukin 16, TRAK2, LIN7A, LIN7B, LIN7C, AKAP5
Modulator:
Glyburide, Nicorandil, Cesium chloride, Tertiapin-Q, Glibenclamide, ML 133 hydrochloride, Barium chloride
Assays:
Patch clamp
Recommended Reviews:
Kubo et al. (2005) International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels. Pharmacol Rev 57(4):509-526
Data and Applications
Cardiac Ion Channels - Pharmacology of Sotalol
CardioExcyte 96 and 
SyncroPatch 384PE (a predecessor model of SyncroPatch 384) 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.
Kir2.1 - Pharmacology of Barium
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384) data and applications:
Cells were kindly provided by Charles River.
Screenshots of the PatchControl 384 software showing Kir2.1 current traces in response to a voltage step protocol. Measured on the SyncroPatch 384PE (a predecessor model of SyncroPatch 384) using the whole cell patch methodology and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 93%. The IC50 value of Barium was determined as 6.38 µM (Literature: 16.2 µM, Schram et al. Cardiovasc Res. 2003).
Poster
2015 - High Throughput Automated Patch Clamp of Ion Channels Important in Cardiac Safety and Drug Discovery
SyncroPatch 384PE (a predecessor model of SyncroPatch 384) poster, Chantest Meeting 2015 
(1.9 MB)
2017 - Activation of CFTR channels in absence of internal fluoride using a highly parallel automated patch clamp system
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) poster, BPS Meeting 2017 (1.5 MB)
2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) and 
Patchliner poster, BPS Meeting 2017 (1.7 MB)
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
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) poster, JSPS Meeting 2018 (2.3 MB)
2020 - Automated Patch Clamp System Introducing Simulated Ik1 Into stem cell derived Cardiomycoytes Using Dynamic Clamp
Patchliner poster, 64th Annual Meeting of the Biophysical Society (1.0 MB)
Application Notes
Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) Patchliner CardioExcyte 96 application note (2.3 MB)
Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) application note (1.3 MB)
Cells were kindly provided by Charles River.
Webinars
2018 - HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i), Patchliner and CardioExcyte 96 Oral Presentation
Presenter:
Tim Strassmaier, Nanion Technologies Inc. USA
Source:
Webinar: "CiPA study: Bridging ion channel and myocyte data", September 12, 2018
27.06.2017 | Webinar: New Dynamics in Automated Patch Clamp
Patchliner
This webinar shows new applications on dynamic patch clamp of iPSC-derived cardiomyocytes and introduces an assay on KCa3.1 expressed in erythrocytes
Publications
2020 - Striatal Kir2 K+ channel inhibition mediates the antidyskinetic effects of amantadine
SyncroPatch 768PE (a predecessor model of the SyncroPatch 768i instrument) publication in The Journal of Clinical Investigation (2020)
Authors:
Shen W., Ren W., Zhai S., Yang B., Vanoye C.G., Mitra A., George AL. Jr., Surmeier D.J.
2020 - Automated Dynamic Clamp for Simulation of IK1 in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes in Real Time Using Patchliner Dynamite8
Patchliner and Dynamite8 publication in Current Protocols in Pharmacology (2020)
Authors:
Becker N., Horváth A., De Boer T., Fabbri A., Grad C., Fertig N., George M., Obergrussberger A.
2018 - A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of IK1 Ion Channels in Real-Time
Patchliner publication in Frontiers in Physiology
Authors:
Goversen B., Becker., N., Stölzle-Feix S., Obergrussberger A., Vos M.A., van Veen T.A.B., Fertig N., de Boer T.P.
2017 - L-Type Calcium Channel Inhibition Contributes to the Proarrhythmic Effects of Aconitine in Human Cardiomyocytes
Patchliner publication in PLoS ONE (2017)
Authors:
Wu J., Wang X., Chung Y.Y. Koh C.H. Liu Z., Guo H., Yuan Q., Wang C., Su S., Wei H.
2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Lab Automation (2016)
Authors:
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.
2015 - Novel screening techniques for ion channel targeting drugs
Patchliner, SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and CardioExcyte 96 publication in Channels (2015)
Authors:
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.
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.
2011 - Development of a selective small-molecule inhibitor of Kir1.1, the Renal Outer Medullary Potassium Channel
Patchliner publication in Molecular Pharmacology (2011)
Authors:
Bhave G., Chauder B.A., Liu W., Dawson E.S., Kadakia R., Nguyen T.T., Lewis L.M., Meiler J., Weaver C.D., Satlin L.M., Lindsley C.W., Denton J.S.
2009 - High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1
Patchliner publication in Molecular Pharmacology (2009)
Authors:
Lewis L.M., Bhave G., Chauder B.A., Banerjee S., Lornsen K.A., Redha R., Fallen K., Lindsley C.W., Weaver C.D., Denton J.S.