Modelling mechanotransduction in primary sensory endings

Mechanotransduction is a process fundamental to life. It underpins a variety of sensory modalities from hearing to blood pressure regulation. However, the molecular components of the mechanosensory mechanisms in primary sensory endings are poorly understood. Experimental approaches to solving this problem are long and laborious. Therefore, a theoretical approach was proposed as an efficient means to circumventing this process. A mathematical, biophysical model of mechanosensory endings was implemented, which reproduced existing experimental data of the receptor potential of the mammalian muscle spindle primary ending. This probabilistic model combines mathematical representations of different ion channel types to produce an output which is the predicted receptor potential of the sensory ending, given the presence of specific ion channels. The model outputs the tension-dependent electrical response of the receptor, given a stretch stimulus. The parameters required for this model identify the necessary molecular entities required for this behaviour to occur. The dbd (dorsal bipolar dendritic) neuron in D. melanogaster larvae fulfils a similar role to the muscle spindle in mammals. Electrophysiological data was obtained from these neurons via whole-cell patching. It was shown that the dbd neuron can respond to both electrical and mechanical stimuli, but that these responses are noticeably distinct. Furthermore the stretch-evoked data obtained from these receptors was equivalent to that predicted by the model, demonstrating a cross-taxa correlation between the behaviour of neurons in this class. This finding enables simple genetic assays to be carried out in D. melanogaster to ascertain the identity of molecules which are involved in primary mechanotransduction at the sensory terminal. A simple bioinformatics search has yielded a shortlist of candidates which fulfill the criteria of the model predictions. These can now be experimentally tested in a simple and direct approach.