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A brief history of trp: commentary and personal perspective

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Abstract

The history of the discovery of the transient receptor potential (TRP) cation channel superfamily began in 1969 with Cosens and Manning's isolation of the Drosophila transient receptor potential mutant, in which the photoreceptor response decays during continuous illumination. Early studies from Minke found that the elementary light response was unaffected in trp mutants, and he attributed the defect to an intermediate stage of phototransduction. Montell and Rubin cloned the trp gene in 1989: they recognised it as a transmembrane protein, but also concluded that it did not encode the light-sensitive channels. In 1991, Minke and Selinger proposed that TRP represented a Ca2+ transporter required for refilling intracellular InsP3-sensitive Ca2+ stores, in turn required for activation of the light-sensitive channels. Also in 1991, after developing a photoreceptor patch clamp preparation, I showed that the light-sensitive channels themselves were highly permeable to Ca2+, questioning the need for such a dedicated Ca2+ transporter. In 1992, in collaboration with Minke, I resolved this paradox by showing there were two classes of light-sensitive channels, one highly Ca2+ permeable and eliminated in trp mutants. This represented the first and compelling evidence that TRP represented a light-sensitive channel and was supported by the cloning of the second light-sensitive channel, TRPL, by Kelly's lab. Three years later, in 1995, the labs of Montell and Birnbaumer independently cloned TRPC1, the first of 29 vertebrate TRP isoforms distributed amongst seven subfamilies.

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Notes

  1. After it became possible to make higher resolution whole-cell voltage clamp patch recordings, quantum bumps in null trp mutants were, in fact, found to be 3–4× smaller than the wild type [21, 42]. Apart from using noise analysis of intracellular voltage recordings, Minke's findings in this respect may also have been compromised by his unwitting use of a trp allele that was not null [34]—although he reported similar results in wild-type flies using La3+, which completely blocks the TRP channel [51].

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  1. Department of Physiology, Development and Neuroscience, Cambridge University, Downing Street, Cambridge, CB2 3DY, UK

    Roger C. Hardie

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Hardie, R.C. A brief history of trp: commentary and personal perspective. Pflugers Arch - Eur J Physiol 461, 493–498 (2011). https://doi.org/10.1007/s00424-011-0922-9

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