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Zhu MX, editor. TRP Channels. Boca Raton (FL): CRC Press; 2011.

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TRP Channels.

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As a rapidly expanding area of research, studies on transient receptor potential (TRP) channels have undergone several interesting stages of historical development. It all started in the 1960s with the identification of a mutant fruit fly strain that lacked the sustained phase of the light response,1 as measured using electroretinography. This technique has been used to record the electrical responses of cells in the retina, including the photoreceptors, to light illumination. These responses have been referred to as the “receptor potential.” The short-lived, or transient, receptor potential to prolonged illumination in the mutant fly gave rise to the name, transient receptor potential (trp), which describes the mutant phenotype. It was not until 1989 when the genetic sequence, which was deleted in the trp mutant, was determined and shown to be a membrane protein with predicted structural similarities to voltagegated ion channels.2,3 Soon after, the Drosophila TRP protein was shown to form a light-induced nonselective cation channel, with higher Ca2+ permeability than Na+, in the insect’s photoreceptor cells.4

That TRP forms a Ca2+-permeable channel downstream from the light response in insect eyes attracted a great deal of attention from investigators working in the areas of mammalian signal transduction. This is because, unlike phototransduction in vertebrates, insects utilize the Gq/phospholipase C pathway for the light response. Many hormones and neurotransmitters in the mammalian system also exert their actions through Gq/11 proteins and phospholipase C and an important signaling event of this pathway is the rise in intracellular Ca2+ concentrations. This occurs through both Ca2+ release from internal stores and Ca2+ influx from the extracellular space. Because of the similarity between the Drosophila phototransduction and the mammalian phospholipase C pathway, it was thought that a mammalian homolog(s) of the TRP channel might fulfill the rule of Ca2+ influx downstream from the activation of phospholipase C. Indeed, the search for the mammalian TRP homolog yielded not one, but seven, nonallelic TRP (now renamed TRP canonical or TRPC) genes in mammals.5 Results from functional studies of heterologously expressed mammalian TRPC isoforms are consistent with a role in Ca2+ influx following phospholipase C activation. However, controversies exist as to whether TRPCs contribute to the formation of store-operated channels and in particular the highly Ca2+ selective type that conducts the so-called Ca2+ release-activated Ca2+ current. Although this is not a focus of the present volume, Chapters 2 and 3 contain considerable discussion on the potential roles of TRPCs and Orai proteins in receptor and store-operated Ca2+ entry. Other functions of TRPC channels, whether related or not to store-operated Ca2+ entry, have also been demonstrated, and some examples can be found in Chapters 4, 9, 10, and 17.

More interesting spins of the TRP field came about from several independent discoveries made by either functional cloning or genetic searches for disease-causing genes in humans during the late 1990s, right after the cloning of mammalian TRPCs, and which subsequently led to the rapid expansion of the field. Among them, the identification of TRPV1, or vanilloid receptor 1, attracted much attention because of its primary involvement in thermal sensation and nociception.6 As such, TRPV1 has been the most studied TRP channel in recent years. TRPV1 was identified as the protein essential for the Ca2+ response to stimulation by capsaicin, a known potent agonist that causes pain. The derived sequence showed homology to the Drosophila TRP and its mammalian homologs, the TRPCs. Likewise, TRPV5, TRPV6, TRPM1, TRPP2, and TRPML1 were identified on the basis of their functions and involvement in diseases. Only after the resolution of the protein sequences was it realized that they also share homology with the Drosophila TRP protein. However, for a few years after the elucidation of these sequences, various names were given to different TRPs and sometimes multiple names were used for the same channel. Therefore, in 2002, a collective effort was made to unify or standardize the nomenclature of these related channel proteins.7 The term TRP superfamily was defined to include the six distantly related subfamilies (seven in invertebrates), namely, TRPC, TRPV, TRPM, TRPA, TRPP, TRPML, and TRPN (invertebrates). To date, 28 TRP members have been described for mammalian species, making it a rather large superfamily of channel proteins with diverse functions. In the meantime, studies on invertebrate TRPs (Drosophila and Caenorhabditis elegans) continue to thrive, offering important insights on the physiological functions of these channels.

The rapid expansion of the TRP field has generated much excellent original work and many review articles. However, what is lacking is a comprehensive coverage of methodology for studying these channels. This volume is intended to fill this gap by providing broad coverage of current methods and techniques commonly used in TRP channel research. Because of the functional and sequence diversity, as well as the different physiological roles they play, techniques used for studying TRP channels are very diverse ranging from single molecular analysis to behavioral animal studies. Methods in multiple areas, such as molecular biology, fluorescence imaging, electrophysiology, cell biology, genetics, proteomics, pharmacology, system physiology, and behavioral assessment, are employed to investigate various aspects of these channels. For this reason, choosing among many possible topics in these broad areas was a daunting task. Our intent is to provide coverage of the major techniques currently used for TRP channel research in diverse areas and also to present a comprehensive viewpoint on the current standing of the field. The majority of the chapters are protocol oriented, with the goal of providing clear directions for laboratory use. Because of the breadth of the TRP field, the applications of some methods are described in multiple chapters by experts working on a variety of channel types that serve different physiological functions. This was intentional as it highlights diverse views on how the methodology can be utilized. Some chapters include discussion not only on the usefulness but also on the pitfalls associated with the use of certain techniques. This should also be of value, and together with chapters that offer comprehensive reviews on the functional regulation and diverse roles of TRP channels, students and investigators new to the field should find this book particularly informative.

Finally, we would like to thank all contributors for their enthusiastic and timely response in preparing chapters. We believe that this volume will be an excellent resource for all investigators in the TRP and related fields.


Cosens D. J, Manning A. Abnormal electroretinogram from a Drosophila mutant. Nature. 1969;224:285–287. [PubMed: 5344615]
Montell C, Rubin G. M. Molecular characterization of the Drosophila trp locus: A putative integral membrane protein required for phototransduction. Neuron. 1989;2:1313–1323. [PubMed: 2516726]
Wong F, Schaefer E. L, Roop B. C, LaMendola J. N, Johnson-Seaton D, Shao D. Proper function of the Drosophila trp gene product during pupal development is important for normal visual transduction in the adult. Neuron. 1989;3:81–94. [PubMed: 2482778]
Hardie R. C, Minke B. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron. 1992;8:643–651. [PubMed: 1314617]
Zhu M. X, Jiang M, Peyton M. et al. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell. 1996;85:661–671. [PubMed: 8646775]
Caterina M. J, Schumacher M. A, Tominaga M, Rosen T. A, Levine J. D, Julius D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature. 1997;389:816–824. [PubMed: 9349813]
Montell C, Birnbaumer L, Flockerzi V. et al. A unified nomenclature for the superfamily of TRP cation channels. Molecular Cell. 2002;9:229–231. [PubMed: 11864597]
Copyright © 2011 by Taylor and Francis Group, LLC.
Bookshelf ID: NBK92809
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