oa Editorial [Hot topic: TRP Channels: From Understanding to Action (Guest Editor: Viktorie Vlachova)]

It is my pleasure to introduce this “Hot Topic” special issue of Current Pharmaceutical Biotechnology, focusing on the family of cation channels that have attracted considerable attention and research work during the past decade as a target class for drug discovery. These channels are called the ‘transient receptor potential’ (TRP) ion channels because deletion of the trp gene, initially discovered in a fruit fly, caused the photoreceptor potential in response to steady light to switch from sustained into transient. Mammalian TRP channels are encoded by 28 genes and can be classified into six main subfamilies: canonical (TRPC), vanilloid (TRPV), melastatin (TRPM), ankyrin (TRPA), polycystin (TRPP), and mucolipin (TRPML) (for nomenclature, please see [1], and references therein). Along with classical ligand-binding mechanisms, TRP channels are able to detect and transduce environmental inputs, such as temperature, light, osmotic pressure, cell membrane deformation or depolarization. These unique activation properties make them ideal candidates for being directly involved in sensory modalities: vision, temperature reception, olfaction, osmosensation, hearing, voltage, taste and nociception. Indeed, the cloning of temperature sensitive members of the TRPV, TRPA or TRPM channel subfamilies from mammalian sensory ganglion cDNA libraries has provided clues to the proteins that detect and evaluate particularly those stimulus modalities that may damage or threaten to damage tissue. In this special issue, we hope to offer readers an informative yet concise insight into the exciting field of research on TRP channels, highlighted from different experts. Their reviews detail current insights into the inner workings of these remarkable channels and deal with recent advances and hurdles that must be overcome when considering TRP channel agonists, antagonists or modulators for future therapeutic evaluation. The modalities of activation of TRP channels are diverse, but they do have something in common: their transmembrane domains have similar architecture, determined by similar physical principles, in particular in terms of the permeability and selectivity of cations, gating the pore and sensing voltage. Víctor M. Meseguer, Bristol L. Denlinger and Karel Talavera focus their review on a number of methodological considerations that are essential to be taken into account when studying the role of TRP channels as sensors and integrators of chemical stimuli. Accumulated evidence suggests that, in addition to the TRP channels localized on the plasma membrane, intracellularly localized TRP channels also actively participate in regulating membrane traffic, vesicular ion homeostasis and signal transduction. The features of the TRP-residing compartments and the processes related to TRP channel trafficking and their insertion into the plasma membrane are highlighted by the article of Carlos A. Toro, Luis A. Arias and Sebastian Brauchi. Primary afferent neurons supplying the gastrointestinal tract can be sensitized in response to pro-inflammatory mediators, and so the mechanisms whereby hypersensitivity is initiated and maintained are of prime therapeutic interest. Although TRP channels contribute to sensory transduction in every region of the body, they play a particular role in the alimentary canal. This special position derives from their function as molecular sensors for distinct chemical and physical modalities that are rather specific to the digestive system. The role of TRP channels in these processes is reviewed by Peter Holzer. The canonical TRPC channels (TRPC1-7) share the common property of activation through phospholipase C-coupled receptors. Christian Harteneck and Maik Gollasch focus on the mechanisms of pharmacological modulation in the specific subclass of TRPC channels, TRPC3/6/7, which are also gated by direct exposure to diacylglycerols. The authors discuss a broad number of drugs that interfere with TRPC3/6/7 activity and function.....