Abstract
Purpose: :
We analyze the photonresponse in the fly photoreceptor using a computational model of biochemical reactions starting with the activation of the opsin. Since the direct messenger to the TRP is still not identified, we proposed here some binding rules at the TRP channel leading to a normal photoresponse. We estimated the mean and variance of the number of DAG, TRP channels open during the response.
Methods: :
Biophysical Modeling and Stochastic Simulations and comparison with electrophysiological data.
Results: :
The fly photonresponse requires the activation of few TRP channels located on each microvilli. To estimate the number of open TRPs, we use Brownian simulations of each molecule involved in the cascade of chemical reactions from the opsin to the TRP channels.We developed a simulation tool using the spatial structure of the microvilli. This simulation allows us to compute the time course of the photonresponse, the number of DAG molecules produced and the number of open TRP channels. We identified the rules for the number of bound DAG and calcium ions involved directly in the opening of the TRP-complex.Our analysis can reproduce recent electrophysiological data obtained in collaboration with the group of B. Minke, leading to a bistability behavior. Indeed under the molecular rules we identified, our modeling agrees with and can reproduce the phenomenological observation that as the outer calcium influx decreases, the photonresponse increases, while the spontaneous bump decreases.
Conclusions: :
Our results suggest that at least 2 DAG molecules should bind to a TRP channel complex in order for our model to account for the photoreceptor bistability, generated by changing the external calcium concentration.
Keywords: photoreceptors • signal transduction • calcium