title: Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons.
abstract: Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch. Receptor potential changes in dbd neurons in response to stretch showed a complex, dynamic profile with similar characteristics to those previously observed for mammalian muscle spindles. These profiles were reproduced by a general in silico model of stretch-activated neurons. This in silico model predicts an essential role for a mechanosensory cation channel (MSC) in all aspects of receptor potential generation. Using pharmacological and genetic techniques, we identified the mechanosensory channel, DmPiezo, in this functional role in dbd neurons, with TRPA1 playing a subsidiary role. We also show that rat muscle spindles exhibit a ruthenium red-sensitive current, but found no expression evidence to suggest that this corresponds to Piezo activity. In summary, we show that the dbd neuron is a stretch receptor and demonstrate that this neuron is a tractable model for investigating mechanisms of mechanotransduction.
authors.affiliation: Doctoral Training Centre in Neuroinformatics and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Suslak
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Sonia
authors.initials: S
authors.lastname: Watson
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Thompson
authors.affiliation: Institute for Ageing, University of Newcastle, Newcastle, United Kingdom.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Shenton
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Guy S
authors.initials: GS
authors.lastname: Bewick
authors.affiliation: Doctoral Training Centre in Neuroinformatics and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom; Institute for Adaptive and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Armstrong
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jarman
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003198:Computer Simulation; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000502:physiology; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D009470:Muscle Spindles / Q000502:physiology; D011434:Proprioception / Q000502:physiology; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013314:Stress, Mechanical; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; C571430:Piezo protein, Drosophila; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; D000584:Amiloride