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Mitochondrial Membrane Research
Publication Link
2023 – Validation of TREK1 ion channel activators as an immunomodulatory and neuroprotective strategy in neuroinflammation
Port-a-Patch mini Publication in Biol. Chem. (2023) Authors: Schroeter C.B., Nelke C., Schewe M., Spohler L., Herrmann A.M., Müntefering T., Huntemann N., Kuzikov M., Gribbon P., Albrecht S., Bock S., Hundehege P., Neelsen L.C., Baukrowitz T., Seebohm G., Wünsch B., Bittner S., Ruck T., Budde T. Meuth S.G.

Modulation of two-pore domain potassium (K2P) channels has emerged as a novel field of therapeutic strategies as they may regulate immune cell activation and metabolism, inflammatory signals, or barrier integrity. One of these ion channels is the TWIK-related potassium channel 1 (TREK1). In the current study, we report the identification and validation of new TREK1 activators. Firstly, we used a modified potassium ion channel assay to perform high-throughput-screening of new TREK1 activators. Dose-response studies helped to identify compounds with a high separation between effectiveness and toxicity. Inside-out patch-clamp measurements of Xenopus laevis oocytes expressing TREK1 were used for further validation of these activators regarding specificity and activity. These approaches yielded three substances, E1, B3 and A2 that robustly activate TREK1. Functionally, we demonstrated that these compounds reduce levels of adhesion molecules on primary human brain and muscle endothelial cells without affecting cell viability. Finally, we studied compound A2 via voltage-clamp recordings as this activator displayed the strongest effect on adhesion molecules. Interestingly, A2 lacked TREK1 activation in the tested neuronal cell type. Taken together, this study provides data on novel TREK1 activators that might be employed to pharmacologically modulate TREK1 activity.

Application Note PDF
CiPA- “Identification of cardiac liability in drug discovery using the Port-a-Patch”
Port-a-Patch application note:   Cells were kindly provided by NEXEL and Charles River, USA.  

In 2013 the Cardiac Safety Research Consortium (CSRC), the Health and Environmental Sciences Institute (HESI), and the US Food and Drug Administration (FDA) proposed a paradigm to improve assessment of the proarrhythmic risk of therapeutic compounds. This paradigm, the Comprehensive In-vitro Proarrhythmia Assay (CiPA), was introduced to provide a more complete assessment of proarrhythmic risk by evaluating and implementing currently available high throughput methods. An important part of this is the electrophysiological evaluation of hERG, and also other cardiac channels including NaV1.5 and CaV1.2. The Q&A draft from August 2020 describes how nonclinical assays such as patch clamp can be used as a part of an integrated risk assessment prior to first-in-human studies, and in later stages of clinical development.Following up on hERG and NaV1.5 best practices and calibration standards which have been published recently on automated patch clamp devices, we show here cardiac ion channel recordings from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) or overexpressing cell lines generated with the world’s smallest patch clamp setups: Port-a-Patch and Port-a-Patch mini. Recordings at RT or physiological temperature of hERG recorded from HEK cells, and peak or late INa current recorded from iPSC-CMs or CHO cells are shown. INa-Late was activated by ATX-II and blocked by ranolazine, INa-Peak was blocked by tetracaine in a concentration-dependent manner, and hERG was blocked by increasing concentrations of dofetilide.

Product video
Port-a-Patch mini Product Video-2019
Do you want to patch a cell in 60 seconds?

The Port-a-Patch mini is built on the success of the Port-a-Patch. We miniaturized this patch clamp system even further by integrating the amplifier into the system. Supporting giga-seal recordings from one cell at a time, the Port-a-Patch mini offers fast and easy access to high quality patch clamp data with only minimal training. Not only a powerful research tool but also ideal for educational purposes and quick tests of cells and ion channels.
Available at an attractive price, the Port-a-Patch mini is a powerful research tool for studying ion channels and also the ideal technology platform for teaching basic electrophysiological concepts in academic institutions.

Product Sheet PDF
Port-a-Patch mini – Product Sheet

How can we help you?

Contact our specialist Dr. Patrick Mumm (Product Manager of the Port-a-Patch family). Patrick is delighted to help you:
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