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Originally cloned as a prostate-specific protein, TRPM8 is now best known as a cold- and menthol-activated channel implicated in thermosensation. In this chapter we provide a brief review of current knowledge concerning the biophysical properties, gating mechanisms, pharmacology and (patho)physiology of this TRP channel.

The TRPA1 protein has up to 18 N-terminal and presumed cytoplasmic ankyrin repeats followed by the six membrane spanning and single pore-loop domains characteristic of all TRPs. In mice, TRPA1 is almost exclusively expressed in nociceptive neurons of peripheral ganglia and in all the mechanosensory epithelia of inner ear. In nociceptive neurons, TRPA1 mediates the response to the proalgesic bradykinin as well as the response to pungent irritants found in mustards and garlic, and probably also to those found in cinnamon and tear gas. The channel properties of TRPA1 are discussed and compared to those of sensory transducers. TRPA1 is well conserved across the animal kingdom, with likely orthologs from human to nematode, which suggest an ancestral role for this channel, probably in sensation.

Polycystin-2, or TRPP2 according to the TRP nomenclature, is encoded by , a gene mutated in patients with autosomal-dominant polycystic kidney disease. Its precise subcellular location and its intracellular trafficking are a matter of intense debate, although a consensus has emerged that it is located in primary cilia, a long-neglected organelle possibly involved in sensory functions. Polycystin-2 has a calculated molecular mass of 110 kDa, and according to structural predictions it contains six membrane-spanning domains and a pore-forming region between the 5th and 6th membrane-spanning domain. This section first introduces the reader to the field of cystic kidney diseases and to the gene, before the ion channel properties of polycystin-2 are discussed in great detail.

On the basis of their ever-expanding roles, not only in sensory signaling but also in a plethora of other, often Ca-mediated actions in cell and whole body homeostasis, it is suggested that mutations in TRP channel genes not only cause disease states but also contribute in more subtle ways to simple and complex diseases. A survey is therefore presented of diseases and syndromes that map to one or multiple chromosomal loci containing TRP channel genes. A visual map of the chromosomal locations of TRP channel genes in man and mouse is also presented.

Orchestrated ion fluctuations within pancreatic islets regulate hormone secretion and may be essential to processes such as apoptosis. A diverse set of ion channels allows for islet cells to respond to a variety of signals and dynamically regulate hormone secretion and glucose homeostasis (reviewed by ). This chapter focuses on transient receptor potential (TRP)-related channels found within the beta cells of the islet and reviews their roles in both insulin secretion and apoptosis.

Ca entry forms an essential component of platelet activation; however, the mechanisms associated with this process are not understood. Ca entry upon receptor activation occurs as a consequence of intracellular store depletion (referred to as store-operated Ca entry or SOCE), a direct action of second messengers on cation entry channels or the direct occupancy of a ligand-gated P2 receptor. The molecular identity of the SOCE channel has yet to be established. Transient receptor potential (TRP) proteins are candidate cation entry channels and are classified into a number of closely related subfamilies including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin) and TRPML (mucolipins). From the TRPC family, platelets have been shown to express TRPC6 and TRPC1, and are likely to express other TRPC and other TRP members. TRPC6 is suggested to be involved with receptor-activated, diacyl-glycerol-mediated cation entry. TRPC1 has been suggested to be involved with SOCE, though many of the suggested mechanisms remain controversial. As no single TRP channel has the properties described for SOCE in platelets, it is likely that it is composed of a heteromeric association of TRP and related subunits, some of which may be present in intracellular compartments in the resting cell.

TRP proteins form ion channels that are activated following receptor stimulation. Several members of the TRP family are likely to be expressed in lymphocytes. However, in many studies, messenger RNA (mRNA) but not protein expression was analyzed and cell lines but not primary human or murine lymphocytes were used. Among the expressed TRP mRNAs are TRPC1, TRPC3, TRPM2, TRPM4, TRPM7, TRPV1, and TRPV2. Regulation of Ca entry is a key process for lymphocyte activation, and TRP channels may both increase Ca influx (such as TRPC3) or decrease Ca influx through membrane depolarization (such as TRPM4). In the future, linking endogenous Ca/cation channels in lymphocytes with TRP proteins should lead to a better molecular understanding of lymphocyte activation.

Mast cells are tissue-resident immune effector cells. They respond to diverse stimuli by releasing potent biological mediators into the surrounding tissue, and initiating inflammatory responses that promote wound healing and infection clearance. In addition to stimulation via immunological routes, mast cells also respond to polybasic secretagogues and physical stimuli. Each mechanism for mast cell activation relies on the influx of calcium through specific ion channels in the plasma membrane. Recent reports suggest that several calcium-permeant cation channels of the TRPV family are expressed in mast cells. TRPV channels are a family of sensors that receive and react to chemical messengers and physical environmental cues, including thermal, osmotic, and mechanical stimuli. The central premise of this review is that TRPVs transduce physiological and pathophysiological cues that are functionally coupled to calcium signaling and mediator release in mast cells. Inappropriate mast cell activation is at the core of numerous inflammatory pathologies, rendering the mast cell TRPV channels potentially important therapeutic targets.

In signal transduction of metazoan cells, transient receptor potential (TRP) ion channels have been identified that respond to diverse external and internal stimuli, among them osmotic and mechanical stimuli. This chapter will summarize findings on the TRPV subfamily, both its vertebrate and invertebrate members. Of the six mammalian TRPV channels, TRPV1, -V2, and -V4 were demonstrated to function in transduction of osmotic and/or mechanical stimuli. TRPV channels have been found to function in cellular as well as systemic osmotic homeostasis in vertebrates. Invertebrate TRPV channels, five in and two in , have been shown to play a role in mechanosensation, such as hearing and proprioception in and nose touch in , and in the response to osmotic stimuli in . In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue mechanosensory and osmosensory deficits of the TRPV mutant line in , despite no more than 26% orthology of the respective amino acid sequences.

Pain is initiated when noxious stimuli excite the peripheral terminals of specialized primary afferent neurons called nociceptors. Many molecules are involved in conversion of the noxious stimuli to the electrical signals in the nociceptor endings. Among them, TRP channels play important roles in detecting noxious stimuli.