TRPs in the Brain
The Transient receptor potential (TRP) family of cation channels is a large protein family, which is mainly structurally uniform. Proteins consist typically of six transmembrane domains and mostly four subunits are necessary to form a functional channel.
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Abstract The Transient receptor potential (TRP) family of cation channels is a large protein family, which is mainly structurally uniform. Proteins consist typically of six transmembrane domains and mostly four subunits are necessary to form a functional channel. Apart from this, TRP channels display a wide variety of activation mechanisms (ligand binding, G-protein coupled receptor dependent, physical stimuli such as temperature, pressure, etc.) and ion selectivity profiles (from highly Ca2+ selective to non-selective for cations). They have been described now in almost every tissue of the body, including peripheral and central neurons. Especially in the sensory nervous system the role of several TRP channels is already described on a detailed level. This review summarizes data that is currently available on their role in the central nervous system. TRP channels are involved in neurogenesis and brain development, synaptic transmission and they play a key role in the development of several neurological diseases.
1 The Transient Receptor Potential Family of Cation Channels The transient receptor potential (TRP) multigene superfamily encodes integral membrane proteins that function as ion channels. Members of this family are conserved in yeast, invertebrates and vertebrates. All members TRP channels are subdivided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (poly-cystin), TRPML (mucolipin), TRPA (ankyrin) and TRPN (NOMPC-like), which is only found in invertebrates. Of the 6 mammalian subfamilies, 28 members are known, with only 27 in humans (TRPC2 is a pseudogene; see Fig. 1) (Nilius and Owsianik 2011). R. Vennekens (*), A. Menigoz and B. Nilius Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine (CMM), KU Leuven, Herestraat 49 (bus 802), BE-3000 Leuven, Belgium e-mail: [email protected] Rev Physiol Biochem Pharmacol, doi: 10.1007/112_2012_8 # Springer-Verlag Berlin Heidelberg 2012
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Fig. 1 Phylogenetic tree of the transient receptor potential family of ion channels. TRPC (canonical), TRPM (melastatin), TRPV (vanilloid), TRPA (ankyrin), TRPP (polycistin) and TRPML (mucolopid). TRPC2 is a pseudogene in humans. The TRP channels reported to be expressed in brain are indicated in bold
It is clear from the current state of the literature that almost all 28 members of mammalian TRP channel play a key role in establishing the five classical senses described in De Anima (book II, 350 B.C.) by Aristotle, which allow humans to perceive the outside world: sight (visus), hearing (auditus), smell (olfactus), taste (gustus) and touch (contactus). For instance, recent studies have firmly established the role of temperature-sensitive TRPs (thermoTRPs) as the principal molecular thermometers in the peripheral sensory system, and provided the first molecular insight into the mechanisms underlying the exquisite thermo- and chemosensitivity of these channels. However, also for balance (or equilibrioreception), which is now
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