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

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.

Kir2.1 - Pharmacology of Barium

CiPA PE Kir2 1icon sp96   SyncroPatch 384/768 PE 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 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

Application Notes

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)

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.

Publications

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

icon pl  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

icon pl  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

icon sp96  SyncroPatch 384PE 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

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE and   Icon CE   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?

icon sp96  SyncroPatch 384PE publication in Journal of Laboratory Automation (2014)

Authors: 
Farre C., Fertig N.

2009 - High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1

icon pl  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.

Webinars

27.06.2017 | Webinar: New Dynamics in Automated Patch Clamp

icon pl   Patchliner

This webinar shows new applications on dynamic patch clamp of iPSC-derived cardiomyocytes and introduces an assay on KCa3.1 expressed in erythrocytes

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