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15.09 - 17.09.2021 | The 4th International TRP Meeting (hybrid edition)

210915 Event image TRP 2021

Conference Venue: Hybrid / Leuven, Berlgium
Go to the Conference website here

Dr. Alison Obergrussberger (Nanion Technologies GmbH) will present the following poster:

"Pharmacology of Transient Receptor Potential cation (TRP) channels using different activation stimuli"

Abstract

Transient Receptor Potential (TRP) channels are distributed throughout the mammalian nervous systems. They can be directly activated by ligands, heat or cold and mechano-stimulation, and are important targets in drug discovery (e.g. pain). We studied the responses of TRPA1, TRPV1, 3 and 4, and TRPM8 assay-ready and cultured cells activated using a variety of stimuli on automated patch clamp (APC) systems.

TRPA1 and TRPM8 are crucial in sensing noxious cold and inflammatory pain, with their antagonists considered promising for the treatment of acute and chronic pain. Desensitization is a key challenge for drug screening of TRPA1 channels. Here, we compare IC50s obtained with long vs short ligand exposure using a high throughput device (SyncroPatch 384). TRPM8 was repetitively cold-activated using a temperature-controlled perfusion system (Port-a-Patch) and blocked by capsazepine.

The TRPV1, 3 and 4 channels are ligand-gated, non-selective cation channels involved in nociception, and respond to elevated temperatures and compounds. Identifying compounds with differential effects on ligand vs heat activation may be crucial in the discovery of new treatments for pain with fewer side effects. Here, we developed robust methods for temperature and pharmacological activation to study the differential effects of blockers. We used ligand activation (capsaicin, 2-APB, GSK1016790) and repeated heat activation of TRPV1, 3, 4 (Patchliner heated pipette, 37-45°C) followed by the addition of blockers. TRPV4 was activated by heat (38°C) and partially blocked by ruthenium red on the Port-a-Patch. In summary, we established a range of reliable automated approaches to study temperature vs pharmacological influences on TRP channels.


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