• Nanion技术: 离子通道研究的智能工具

    Nanion技术: 离子通道研究的智能工具

  • SyncroPatch 384i: HTS Automated Patch Clamp

    SyncroPatch 384i: HTS Automated Patch Clamp

  • SURFE²R 96SE: 非标记高通量转运体筛选

    SURFE²R 96SE: 非标记高通量转运体筛选

  • Dynamic Clamp: Patchliner

    Dynamic Clamp: Patchliner

  • 脂双层记录: Orbit产品系列

    脂双层记录: Orbit产品系列

  • CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

    CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

我们的产品目录

SyncroPatch 384

SyncroPatch 384

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16 TC

Orbit 16 TC

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

15.10.2020 | Webinar: Evaluation of possible proarrhythmic potency: variability of IC50 values of drugs under different conditions and in different platforms

 icon pl Patchliner Webinar

Date: October 15. 2020

201012 Blog Image VUM 2020

Speakers:

Dr. Péter Orvos (University of Szeged)


This is an on-demand webinar from Nan]i[on and Friends 2020.

Abstract:

The conventional microelectrode technique and the manual patch clamp method offer direct, information-rich, and real-time in vitro technologies to study proarrhythmic effect of drugs and drug candidate compounds. Although providing excellent data quality, these tests are complicated, time consuming and expensive for the large numbers of compounds. Automated patch-clamp platforms are mainly used with stably expressing cell lines and suitable for rapid and high-quality pharmacological investigation of drug candidates. The Comprehensive in Vitro Proarrhythmia Assay (CiPA) was initiated to further improve these preclinical drug safety paradigms. However, some evidence indicates that the different proarrhythmic pharmacological assays result in contradictory outcomes raising serious questions regarding their predictability for in vivo situations including clinical settings. IC50 values may varied between platforms, therefore, aim of our study was to compare the effect of proarrhythmic compounds on hERG and IKr currents and on cardiac action potential. The hERG current was measured by using both automated and manual patch clamp methods on HEK293 cells. The native ion current (IKr) were recorded from rabbit ventricular myocytes by manual patch clamp technique.

Dofetilide, cisapride, sotalol, terfenadine and verapamil were tested in hERG assay at both room temperature and 37°C with Patchliner. All these compounds were more potent at physiological temperature and therefore, it is a desirable option to study hERG currents at physiological temperature. To evaluate the prognostic value of hERG assay these agents were subjected for further investigations. The IKr current blocking capability of the compounds was tested on rabbit ventricular myocytes with manual patch clamp method at 37°C. The corresponding IC50 values of dofetilide, cisapride and verapamil were in good agreement with IC50 values obtained with Patchliner in hERG assays. As sotalol and terfenadine have stronger effect on IKr measured by manual patch clamp method compared with hERG automated patch clamp experiments, the effects of these drugs on hERG current using manual patch clamp technique were also investigated to study how the potency of these drugs are influenced by the experimental techniques themselves. In contrast with the hERG automated patch clamp assays, the effects of sotalol and terfenadine on hERG current were stronger measured by the manual patch-clamp technique.

In conclusion, results obtained with automated patch-clamp equipment in HEK-hERG cells usually show a reasonable conformity with outcomes of IKr current experiments. The Patchliner system used in our study is well suited to perform safety pharmacological studies. Variability of IC50 values of drugs in different platforms observed in certain cases, which could have been caused by the lack of continuous flow of compound-containing solutions. 

 


 

返回总览

 

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.