Study of TRP Channels by Automated Patch Clamp Systems
Ion channels are responsible for the permeation of ions across the membrane and their central role in cellular physiology is well established. Historically, the direct study of ion channels has been considered technically challenging. As such, a significant barrier to drug discovery for ion channels has been the low throughput of high quality electrophysiological data. The emergence of automated high throughput platforms for studying ion channel kinetics and pharmacology has lowered this barrier. Ion channels are now recognized as increasingly important drug targets and a diverse range of ion channels are implicated in a variety of drug discovery and cardiac safety assessment programs. The TRP (Transient Receptor Potential) superfamily of ion channels play a crucial role in a broad range of sensory functions including vision, taste, olfaction, hearing, touch, pain and thermosensation. Many of the TRP channels are polymodal in their activation and deactivation mechanisms and even with conventional patch clamp electrophysiology, the TRP channels are considered to be a very complex target class. Here we present an update on the significant progress made on the TRP receptor assays with the available automated patch clamp systems.
KeywordsTransient Receptor Potential Patch Clamp Transient Receptor Potential Channel Trouble Asset Relief Program Patch Clamp Electrophysiology
The QPatch results presented in this review have been generated by many scientists at Sophion Bioscience. We would especially like to thank Rikke L. Schrøder and Hervør L. Olsen for their contribution with data: Dorthe Nielsen is acknowledged for her expert technical assistance. M. Knirke Jensen and Søren Friis are thanked for providing data and valuable critical input to this manuscript. Many thanks also to Chris Mathes for being an inspirator and scientific mentor during both data and manuscript generation.
We thank AstraZeneca, Sweden, for generously proving the TRPA1, TRPV1, and TRPM8 cell lines. The scientists at Novartis, UK, Pamela Tranter, Mark McPate and Martin Gosling are thanked for sharing their data on TRPM2.
- 3.Korsgaard MP, Strobaek D, Christophersen P (2009) Automated planar electrode electrophysiology in drug discovery: examples of the use of QPatch in basic characterization and high content screening on Na(v), K(Ca)2.3, and K(v)11.1 channels. Comb Chem High Throughput Screen 12:51–63CrossRefPubMedGoogle Scholar
- 7.Clark G, Todd D, Liness S, Maidment SA, Dowler S, Southan A (2005) Expression and characterization of a two pore potassium channel in HEK293 cells using different assay platforms (Abstract). Proceedings of the British Pharmacological Society at http://www.pA2online.org/abstracts/vol3Issue4abst105P.pdf
- 18.McPate M, Lilley S, Gosling M, Friis S, Jacobsen RB, Tranter P (2010) Evaluation of the QPatch HT and HTX systems as methods for ion channel screening (Abstract). Biophys J 98(3):340a–340aGoogle Scholar
- 33.Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y (2002) LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9:163–173CrossRefPubMedGoogle Scholar
- 52.Jiang X (2010) Assay of TRPV4 Channel using PatchXpress 7000A and Ionworks Quattro SystemsGoogle Scholar