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  NOTABLE    

Recent notable publications about hERG
Rapid characterisation of hERG channel kinetics I: using an automated high-throughput system. (2019) Lei C.l., Clerx M., Beattie K.A., et al.

A 15 s voltage protocol was used to characterize the hERG1a channel on the SyncroPatch 384PE and compared with manual patch clamp data. Furthermore, the data was used to parameterise a mathematical model, paving the way for a new era of automated and rapid development of mathematical models from quick and cheap experiments.


Rapid characterisation of hERG channel kinetics II: temperature dependence. (2019) Lei C.l., Clerx M., Beattie K.A., et al.

The temperature-dependence of hERG1a was characterized using the SyncroPatch 384PE equipped with temperature control. Different short, information-rich voltage protocols identified how kinetic parameters change over temperature. Researchers found that commonly-used Q10 and Eyring formulations are incapable of describing the parameters' temperature dependence and a more generalised Eyring relationship works well, but remeasuring kinetics and refitting a model is optimal.


Avoiding hERG-liability in drug design via synergetic combinations of different (Q)SAR methodologies and data sources: a case study in an industrial setting. (2019) Hanser T., Steinmetz F.P., Plante J., Rippmann F., and Krier M.

Different in silico prediction approaches and data sets were combined to investigate hERG liability. The Patchliner was used to generate the private data set which was used to 'train' different statistical models. Good in silico models which have been trained using a combination of public and private data may be important for improving safety assessment reducing late stage failure in the drug discovery process.


Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2. (2019) Bodi I., Sorge J., Castiglione A., et al. 

Postpartum hormones oxytocin and prolactin cause APD90 prolongation in female LQT2 cardiomyocytes by inhibition of IKs-tail and IKs-steady currents. Incorporating the data into in silico models resulted in reduced repolarization reserve and increased propensity to pro-arrhythmic permanent depolarization, lack of capture and early afterdepolarizations formation.
 
  NEWS    
Patchliner Safety Edition, Buffer Solution Portfolio, Job Exchange, SyncroPatch 384PE in the News
 

Buffer Solution Portfolio - secure your 30% discount!

 
Save precious time and buy high quality patch clamp solutions from Nanion for all your patch clamp experiments! We are offering an introductory special offer - receive 30% discount when you order solution kits before the end of the year. Check out our new portfolio in the Product Sheet and order soon to secure your 30% discount!

The SyncroPatch 384PE
in the News

 
"Associate Professor Mirella Dottori and Professor David Adams (Illawarra Health and Medical Research Institute) are using a SyncroPatch 384PE robot which can measure the electrical activity of as many as 384 cells at a time."
"With the help of a revolutionary robot, Professor David Adams and Associate Professor Mirella Dottori are studying neurons, testing drug candidates for chronic pain, and working towards precise, personalised neurological treatment."
Read the full article here

Latest Publications


SyncroPatch 384PE:
Rapid characterisation of hERG channel kinetics I: using an automated high-throughput system.
Lei C.L. et al., BioRxiv (2019)
Download here.

SyncroPatch 384PE:
Rapid characterisation of hERG channel kinetics II: temperature dependence.
Lei C.L. et al., BioRxiv (2019)
Download here.

SyncroPatch 384PE:
High Throughput Characterization of KCNB1 Variants Associated with Developmental and Epileptic Encephalopathy.
Kang S.K. et al., BioRxiv (2019)
Download here.

Port-a-Patch and Orbit mini:
Structure of the human ClC-1 chloride channel.
Wang K. et al., PLoS Biol. (2019)
Download here.

Port-a-Patch and Internal Perfusion:
Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures.
Hammelmann, V. et al., JCI Insight (2019)
Download here.

Port-a-Patch:
Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2.
Bodi, I. et al., EP Europace (2019)
Download here.


CardioExcyte 96:
The patient-independent human iPSC model – a new tool for rapid determination of genetic variant pathogenicity in long QT syndrome.
Chavali, N.V. et al., Heart Rhythm (2019)
Download here.

Snapshot of the Month


Our superhero Patchliner team (left to right) András Horváth, Christian Grad, Nadine Becker and Ali Obergrussberger had fun at a recent in-house photo shooting. Contact them to find out more about the benefits of the Patchliner for your research needs!

Patchliner Safety Edition

 
Get the most out of your cardiac safety experiments with the Patchliner Safety Edition. Equipped with the Patchliner CoolingPlate, Temperature Control and (coming soon) Dynamic Clamp, the Patchliner Safety Edition comes with pre-loaded acquisition and analysis routines and SOPs for CiPA-specified ion channels, and a safety pharmacology-focussed installation and training by one of our highly trained electrophysiologists. Find out more about the Patchliner Safety Edition in our Product Flyer.  

Job Exchange


Nanion Technologies, Inc. (Livingston, USA): Application Scientist (Bilayer). Apply here.

Nanion Technologies, Inc. (San Francisco Bay Area, USA): Field Service Engineer. Apply here.

Broad Institute of MIT and Harvard (Cambridge, USA): Research Scientist I, looking for a scientist using the SyncroPatch 384PE. Apply here.

RWTH Aachen University Hospital (Germany): PhD student - Topic: Hereditary pain. Apply here.

Victor Chang Cardiac Research Institute (Sydney, Australia): Lead Scientist - Cell Phenotyping (using the SyncroPatch 384PE). Apply here.

Mark Your Calendar


16. - 20. June 2019:
The 7th International Ion Channel Conference
(Hangzhou, China). Meet Andy Di, Lance Liu and Elena Dragicevic.

17. - 20. June 2019:
18th Annual World Preclinical Congress
(Boston, USA). Meet Ronald Knox.

22. - 25. June 2019:
9th Annual China Meeting on Drug Toxicology
(Wuhan, China). Meet Andy Di.

22. - 26. June 2019:
European Workshop in Bacterial Protein Toxins (ETOX 19)
(Davos, Switzerland). Meet Conrad Weichbrodt.

26. - 29. June 2019:
ISSCR 2019 Annual Meeting
(Los Angeles, USA). Meet Ronald Knox.

07. July 2019:
Cellular mechanisms of anti-cancer induced cardiotoxicity
(Aberdeen, United Kingdom). Meet Alison Obergrussberger.

07. - 12. July 2019:
The Ion Channel Regulation Conference: Molecules to Disease
(Lisbon, Portugal). Meet Andrea Brüggemann.

08. - 10. July 2019:
Physiology 2019
(Aberdeen, United Kingdom). Meet Alison Obergrussberger.
  TOPIC    
The potassium currents controllling cardiac repolarization: IKs and IKr
The cardiac action potential

The cardiac action potential begins with an initial depolarization phase (Phase 0) which is primarily due to an inward Na+ current (INa) mediated by NaV1.5. Following minor repolarization due to inactivation of NaV channels and activation of transient outward potassium currents (Ito) (Phase 1), there is a plateau phase (Phase 2) which is dominated by an inward Ca2+ current (ICa). Repolarization (Phase 3), i.e returning the membrane to the resting potential, is principally driven by the opening of voltage-gated K+ channels (KV). IKr (hERG) and IKs  (KCNQ1, also called KVLQT1 or KV7.1) are important in this repolarization phase and are among the principal determinants of AP duration (APD) and, therefore, both the time course of the Ca2+-mediated contraction and the refractory period.
IKr and IKs: Roles in Long QT syndromes and cardiac safety pharmacology

The hERG channel underlies the rapid delayed rectifyer current (IKr) which, together with the slow delayed rectifyer current (IKs), is responsible for repolarization of the cardiac membrane potential following an action potential. Importantly, loss-of-function mutations in either KCNQ1 or the hERG channel cause different types of long QT syndrome (LQTS), inherited disorders associated with an increased risk of cardiac arrhythmia and sudden cardiac death. In addition to this, drugs which block the hERG channel can cause drug-induced arrhythmia and this has led to inclusion of hERG testing in almost all drug development programs. The Comprehensive In Vitro Pro-arrhythmia Assay (CiPA) initiative, started in 2014, is an ongoing project designed to improve drug safety testing. One aspect of this is to extend the ion channel targets for drug testing to include not only hERG but also CaV1.2, NaV1.5Peak, NaV1.5Late, with the view to extending this to also include KCNQ1/KCNE1, KV4.3 and Kir2.1 (see CiPA). We have taken an active part in the CiPA study with the Patchliner and SyncroPatch 384PE to test a blinded set of compounds on IKr, ICa, INaPeak and INaLate. The results are expected to be published soon so stay tuned!

Meet us at the International KV7 Channels Symposium in September to find out more about recording IKs on the Patchliner and SyncroPatch 384PE. 

IKs and IKr: Recommended Assays, Cell Lines and Literature


hERG (IKr) and KCNQ1/KCNE1 (IKs) expressed in cell lines can be recorded using APC instruments using CiPA-recommended protocols at room or physiological temperature. 

Recommended assays:
  • SyncroPatch 384PE (HTS patch clamp): external solution exchange; internal perfusion; temperature control
  • Patchliner (automated patch clamp): external solution exchange; internal solution exchange; temperature control; dynamic clamp
  • Port-a-Patch(automated patch clamp): external perfusion; internal perfusion; temperature control)

Recommended cell lines:

Read hERG Application Notes

Visit our website for more Application Notes!
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