Photoreceptors, Sensor Cells.
Collaboration with G. Fain UCLA, USA
The goal of our research is to model the function of sensor cells from a molecular level. We are currently studying how photoreceptors respond to light. This project requires the modeling of various molecular pathways that determine the physiological conditions under which the cells operate with and without light. Following many studies, we have proposed in the past, a mathematical approach to describe stochastic chemical reactions inside a cell, to quantify the level of the noise and to determine the time course of the photon-response in both cones and rods. Ultimately we wish to explain in what sense cones are noisier than rods, and determine the gain amplification generate by a single photon. This research is not only challenging from a biological perspective but also mathematically, because it requires new analysis. We are interested in how a cone can detect several photons and how the molecular response is amplified.
More generally, we are interested in deriving from a molecular level the physiology of sensor cells. This includes olfactory cells, hair cells,… Another related goal is to elucidate the mechanism of adaptation in cones. This research involves the modeling of chemical reactions in photoreceptors, stochastic equations, partial differential equations, computer simulations, analysis….anything we need to solve the problem.
More about cones and rods
Rods and cones photoreceptors respond to light by an hyperpolarization of the membrane potential. The signal modulated the synapse of the photoreceptors only when the it produces a change in membrane current, that exceeds a certain threshold. Thus this threshold is a fundamental characteristic of the phototransduction process, defined as the amplitude of the spontaneous membrane current and is referred as the ``dark noise’’.
Dark noise has been studied in cones and rods and it has been demonstrated that cones are much noisier in dark (absence of any light) than rods, since the amplitude of the noise is about 0.03pA in rods (in primates) while it is 0 .12 pA in cones. As a consequence, a single photon is detectable by a rod whereas at least 5 to 8 are needed to produce a response in cones. For this reason rods appear to be the ultimate sensitive cell detector that responds to a single photon.
J. Reingruber D. Holcman, Markov model for the first step of phototransduction in cones and rods, to appear in Biophys. J. 2007
D. Holcman J. Korenbrot, The limit of photoreceptor sensitivity; molecular mechanisms of dark current noise in retinal, J Gen Physiol. 2005,125(6):641-60.
D. Holcman, J. Korenbrot. 2004. Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: the consequence of cell structure, Biophysical Journal, 86:2566-2582
J Reingruber, D Holcman, GL Fain, How rods respond to single photons: Key adaptations of a G‐protein cascade that enable vision at the physical limit of perception, BioEssays 37 (11), 1243-1252 2015.
At a molecular level (figure below), the dark noise is due to the fluctuation of the membrane potential generated by all the biochemical events involved in controlling the ionic flow through the cGMP-gated channels. The regulation of the chemical events is an intrinsic property of the cell. Voltage responses of the photoreceptors for different light intensities are given in the figure above. The biochemical reactions are summarized in the figure below
- Pugh-Lamb 1992.