Proceedings of The Physiological Society

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, C13

Oral Communications

Identifying a primary mechanotransducer in a model sensory system

T. Suslak1, A. P. Jarman1, D. Armstrong1

1. University of Edinburgh, Edinburgh, United Kingdom.

Stretch-activated afferent neurons are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. We have developed a novel, in vivo recording protocol to obtain receptor potential recordings from intact dbd sensory neurons, in situ, in larval Drosophila to determine whether these neurons are a tractable model of such receptors for investigating mechanisms of mechanotransduction. Electrophysiological recordings from dbd neurons are shown to be equivalent to those previously obtained from mammalian muscle spindles. Both of these are accurately modelled by an in silico model of stretch-activated neurons that we are developing. Subsequently, this in silico model is shown to predict an essential role for a mechanosensory cation channel in receptor potential generation. We identify the mechanosensory ion channel, Piezo, in this functional role in dbd neurons, using pharmacological and genetic techniques. Here, for the first time, DmPiezo, the only orthologue of the Piezo family in D. melanogaster, has been implicated in a stretch-activation response. This study shows the utility of an in silico model for identifying components of a mechanosensitive system. It also establishes the dbd neuron as a useful, accessible and tractable model for studying the phenomenon of stretch-dependent mechanotransduction. Our study represents the first direct evidence for an in vivo role for Piezo in mechanotransduction. Whilst earlier studies have shown effects of Piezo loss at the behavioural level, or in cultured cells, this is the first time that the contribution of DmPiezo to a cellular mechanism in fully differentiated neurons has been directly demonstrated. As far as we are aware, we have developed the first model system for patch clamp recording of mechanically activated receptor potentials in intact, fully differentiated mechanosensory neurons in a genetically tractable model organism. Whilst earlier studies have utilised electrophysiology of Drosophila afferent neurons, we are unaware of any study which utilises this approach to test in vivo responses to physiological, mechanical stimuli. This is a unique combination of properties in a single system. In combination with mathematical modelling of the receptor potential, with predictive capacity for candidate channel properties, this promises to be a very powerful tool for future studies dissecting the process of mechanotransduction and identifying transducer proteins that are activated by mechanical stimuli in the physiological range.

Where applicable, experiments conform with Society ethical requirements