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Photosensitive TRPs

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Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 223))

Abstract

The Drosophila “transient receptor potential” channel is the prototypical TRP channel, belonging to and defining the TRPC subfamily. Together with a second TRPC channel, trp-like (TRPL), TRP mediates the transducer current in the fly’s photoreceptors. TRP and TRPL are also implicated in olfaction and Malpighian tubule function. In photoreceptors, TRP and TRPL are localised in the ~30,000 packed microvilli that form the photosensitive “rhabdomere”—a light-guiding rod, housing rhodopsin and the rest of the phototransduction machinery. TRP (but not TRPL) is assembled into multimolecular signalling complexes by a PDZ-domain scaffolding protein (INAD). TRPL (but not TRP) undergoes light-regulated translocation between cell body and rhabdomere. TRP and TRPL are also found in photoreceptor synapses where they may play a role in synaptic transmission. Like other TRPC channels, TRP and TRPL are activated by a G protein-coupled phospholipase C (PLCβ4) cascade. Although still debated, recent evidence indicates the channels can be activated by a combination of PIP2 depletion and protons released by the PLC reaction. PIP2 depletion may act mechanically as membrane area is reduced by cleavage of PIP2’s bulky inositol headgroup. TRP, which dominates the light-sensitive current, is Ca2+ selective (P Ca:P Cs >50:1), whilst TRPL has a modest Ca2+ permeability (P Ca:P Cs ~5:1). Ca2+ influx via the channels has profound positive and negative feedback roles, required for the rapid response kinetics, with Ca2+ rapidly facilitating TRP (but not TRPL) and also inhibiting both channels. In trp mutants, stimulation by light results in rapid depletion of microvillar PIP2 due to lack of Ca2+ influx required to inhibit PLC. This accounts for the “transient receptor potential” phenotype that gives the family its name and, over a period of days, leads to light-dependent retinal degeneration. Gain-of-function trp mutants with uncontrolled Ca2+ influx also undergo retinal degeneration due to Ca2+ cytotoxicity. In vertebrate retina, mice knockout studies suggest that TRPC6 and TRPC7 mediate a PLCβ4-activated transducer current in intrinsically photosensitive retinal ganglion cells, expressing melanopsin. TRPA1 has been implicated as a “photo-sensing” TRP channel in human melanocytes and light-sensitive neurons in the body wall of Drosophila.

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  1. Department Physiology Development and Neuroscience, Cambridge University, Cambridge, UK

    Roger C. Hardie

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  1. Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven Department, Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Pharmakologie und Toxikologie, Universität des Saarlandes, Institut für Experimentelle u. Klinische, Homburg, Germany

    Veit Flockerzi

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Hardie, R.C. (2014). Photosensitive TRPs. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_4

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